Articles de revues : « RCC tissues »

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Abu Haeyeh, Yasmine, Mohammed Ghazal, Ayman El-Baz et Iman M. Talaat. « Development and Evaluation of a Novel Deep-Learning-Based Framework for the Classification of Renal Histopathology Images ». Bioengineering 9, n^o 9 (30 août 2022) : 423. http://dx.doi.org/10.3390/bioengineering9090423.

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Kidney cancer has several types, with renal cell carcinoma (RCC) being the most prevalent and severe type, accounting for more than 85% of adult patients. The manual analysis of whole slide images (WSI) of renal tissues is the primary tool for RCC diagnosis and prognosis. However, the manual identification of RCC is time-consuming and prone to inter-subject variability. In this paper, we aim to distinguish between benign tissue and malignant RCC tumors and identify the tumor subtypes to support medical therapy management. We propose a novel multiscale weakly-supervised deep learning approach for RCC subtyping. Our system starts by applying the RGB-histogram specification stain normalization on the whole slide images to eliminate the effect of the color variations on the system performance. Then, we follow the multiple instance learning approach by dividing the input data into multiple overlapping patches to maintain the tissue connectivity. Finally, we train three multiscale convolutional neural networks (CNNs) and apply decision fusion to their predicted results to obtain the final classification decision. Our dataset comprises four classes of renal tissues: non-RCC renal parenchyma, non-RCC fat tissues, clear cell RCC (ccRCC), and clear cell papillary RCC (ccpRCC). The developed system demonstrates a high classification accuracy and sensitivity on the RCC biopsy samples at the slide level. Following a leave-one-subject-out cross-validation approach, the developed RCC subtype classification system achieves an overall classification accuracy of 93.0% ± 4.9%, a sensitivity of 91.3% ± 10.7%, and a high classification specificity of 95.6% ± 5.2%, in distinguishing ccRCC from ccpRCC or non-RCC tissues. Furthermore, our method outperformed the state-of-the-art Resnet-50 model.

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Serth, Jürgen, Inga Peters, Olga Katzendorn, Tu N. Dang, Joana Moog, Zarife Balli, Christel Reese et al. « Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS) ». International Journal of Molecular Sciences 23, n^o 19 (23 septembre 2022) : 11190. http://dx.doi.org/10.3390/ijms231911190.

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Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20–50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10−8–7.5 × 10−3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.

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Pramanik, Sandip, Subhayan Sur, Biswabandhu Bankura, Chinmay Kumar Panda et Dilip Kumar Pal. « Expression of proliferating cell nuclear antigen and Ki-67 in renal cell carcinoma in eastern Indian patients ». International Surgery Journal 6, n^o 10 (26 septembre 2019) : 3687. http://dx.doi.org/10.18203/2349-2902.isj20194425.

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Background: Several molecular markers play important role in development and prognosis of renal cell carcinoma (RCC). Proliferating cell nuclear antigen (PCNA) and Ki-67 are such kind of molecular markers which may have prognostic significance in RCC and need to be studied about. Estimation of proliferation index by immunohistochemical expression analysis of PCNA and Ki-67 at different clinical stages of RCC samples and correlations of expression of the genes with different clinicopathological parameters between tumour tissue cells and adjacent normal tissue cells were the objectives.Methods: Thirty two patients of RCC who had been operated at one tertiary care institute of eastern India were taken for the study. Histopathological and immunohistochemistry analysis of PCNA and Ki-67 from tumour tissue and normal tissue were done. Patients who received radiotherapy, chemotherapy etc. before operation and who had benign tumours of the kidney in histopathological examination were excluded from the study.Results: Mean PCNA expression in normal renal tissue is 4.54%; whereas the clear cell RCC, papillary RCC and chromophobe RCC showed 49.81%, 50.75% and 66.50% of mean PCNA expression respectively. Mean expression of Ki-67 in normal tissues was 1.75%. Whereas the clear cell RCC, papillary RCC and chromophobe RCC showed 23.96%, 24.75% and 31% of mean Ki-67 expression respectively. Both molecular markers were positively correlated overall.Conclusions: PCNA and Ki-67 expression is increased in RCC when compared with normal tissues and it increases with Stage of RCC. PCNA expression is positively correlated with Ki-67 in different stages and histopathological groups of RCC.

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von Klot, Christoph A. J., Natalia Dubrowinskaja, Jörg Hennenlotter, Mario W. Kramer, Axel S. Merseburger, Arnulf Stenzl, Inga Peters, Hossein Tezval, Markus A. Kuczyk et Juergen Serth. « Rho GDP dissociation inhibitor beta ARHGDIB in renal cell cancer. » Journal of Clinical Oncology 33, n^o 7_suppl (1 mars 2015) : 474. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.474.

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474 Background: Rho GDP dissociation inhibitor 2 (ARHGDIB) is an important mediator of cellular signaling. The expression of ARHGDIB correlates with tumor growth and metastasis in a variety of non genitourinary cancers, however the role of ARHGDIB in renal cell cancer (RCC) has not yet been evaluated. Methods: Tissue samples from 106 patients undergoing surgery for RCC were obtained. The expression of ARHGDIB mRNA in normal kidney tissue and in corresponding cancer tissue was analyzed by means of quantitative real time PCR. Differences in mRNA expression levels were assessed using paired two-sample tests. Associations of relative mRNA expression levels and clinicopathological parameters were statistically analyzed using an univariate logistic regression model. Relative mRNA expression levels in healthy renal tissue compared to cancerous tissue from the same kidney was assessed using a paired t-test. Results: When comparing 74 tissues from kidney tumors with adjacent histologically normal appearing paired tissues, mRNA expression of ARHGDIB was significantly higher in the tumor tissue (p < 0.001). Paired analysis did not only show significantly higher mRNA expression levels for ARHGDIB over all RCC but also for the subgroup with clear cell RCC (ccRCC). The mRNA expression of ARHGDIB was also more pronounced in ccRCC when compared with papillary RCC (p < 0.001). When looking at clinicopathological parameters in univariate logistic regression analysis ccRCC was significantly associated with nodal involvement (p = 0.03) and also with tumor grade (p = 0.05). For all RCC there was no association with clinicopathological parameters. A bivariate Cox regression model, adjusted for metastatic status (p = 0.001), tumor diameter (p = 0.043), state of advanced disease (p = 0.030) and lymph node metastasis (p = 0.006) identified ARHGDIB mRNA expression as a candidate positive prognosticator for RFS. Conclusions: Increased ARHGDIB mRNA expression is significantly associated with RCC tissues. Higher relative expression observed within tumor tissues represents a candidate prognosticator for better RFS of patients.

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Liu, Biao, et Liang Zhang. « Radix Actinidia chinensis Suppresses Renal Cell Carcinoma Progression : Network Pharmacology Prediction and In Vivo Experimental Validation ». Analytical Cellular Pathology 2022 (30 juillet 2022) : 1–12. http://dx.doi.org/10.1155/2022/3584445.

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Background. Renal cell carcinoma (RCC) is a frequent disease with limited curative methods. This study is aimed at investigating the role and mechanism of Radix Actinidia chinensis (RAC) on RCC. Methods. The ingredients, target, and crucial pathways of RAC in RCC therapy were analyzed by network pharmacology. Then, an RCC animal model was established by subcutaneously injecting A498 cell suspension to BALB/c nude mice. After 1 week, the mice in the RAC-L/M/H groups were administered with RAC at 5, 10, and 20 mg/kg/d, respectively. The histopathology of the tumor was evaluated. The contents of tumor inflammatory cytokines and serum oxidative stress factors were detected by ELISA. The apoptosis of tumor tissues was assessed by TUNEL staining. The expressions of apoptosis-, proliferate-, autophagy-, and MAPK-related proteins were measured. Results. There were 13 active ingredients, and 20 RCC-relevant targets were selected from RAC; KEGG pathway indicated that these targets were enriched in the PI3K/AKT/mTOR and MAPK pathway. In in vivo experiments, RAC not only obviously damaged tumor cells and decreased the release of inflammatory cytokines and oxidative stress factors but also enhanced the apoptosis of the tumor cell in RCC mice. Besides, the expressions of apoptosis-, proliferate-, autophagy-, PI3K/AKT/mTOR path-, and MAPK path-related proteins were all affected by RAC. Conclusion. RAC attenuated RCC by regulating inflammation response, oxidative stress, apoptosis, proliferation, and autophagy, and its effects were partly linked to the PI3K/AKT/mTOR and MAPK pathway, which indicated that RAC may be a candidate drug for RCC.

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Zhai, Xiaoqiang, Yan Wu, Zhenlong Wang, Dawei Zhao, Hecheng li, Tie Chong et Jun Zhao. « Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis ». Cell Transplantation 29 (1 janvier 2020) : 096368972096441. http://dx.doi.org/10.1177/0963689720964413.

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Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). In vivo study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.

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Su, Yajuan, Wentao Wang, Yongpeng Xu, Wei Liangjun, Yanjie Wang, Changfu Li et Lichen Teng. « Clinicopathological significance of galectin-1 expression and percentage of galectin-1-expressing T cells in clear-cell renal cell carcinoma ». Canadian Urological Association Journal 12, n^o 5 (25 mars 2018) : E243–9. http://dx.doi.org/10.5489/cuaj.4573.

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Introduction: This study investigates the clinical significance of galectin-1 expression in carcinoma tissues, plasma, and lymphocytes of patients with clear-cell renal cell carcinoma (RCC).Methods: Galectin-1 expression was investigated, using immunohistochemistry, in 91 clear-cell RCC tissue sections, five angioleiolipomas tissue sections, and three oncocytomas tissue sections. As controls, normal tissue sections adjacent to each tumour and six benign renal tumour sections were examined. Plasma galectin- 1 levels as measured by ELISA were compared in 39 patients. Proportions of galectin-1 expressing CD4+ and galectin-1 expressing CD8+ T lymphocytes in peripheral blood of these patients were detected by flow cytometry.Results: The positive expression rate of galetin-1 in 91 clear-cell RCC tissues sections by immunohistochemistry was 87 (95.6%), with weak expression rate of 35.2 (32/91), moderate expression rate of 51.6% (47/91), and strong expression rate of 13.2% (12/91); whereas 25% (2/8) of renal benign tumour sections showed weak galectin-1 expression, 91.2% (83/91) of non-tumor tissues adjacent to carcinomas had negative expression of galectin-1, and another six (75%) renal benign tumour sections had negative galectin-1 expression. Plasma galectin-1 levels between patients with clearcell RCC and with benign tumours were not significantly difference (p>0.05). In patients with clear-cell RCC, we found a significantly higher proportion of galectin-1-expressing CD4+ lymphocytes (p<0.05) and galectin-1-expressing CD8+ lymphocytes (p<0.05) than in patients with benign tumours. Moreover, the level of galectin- 1 expression was positively associated with stage and Fuhrman grade of clear-cell RCC.Conclusions: Our results suggest that high level of galectin-1 expression in clear-cell RCC tissues may be a useful marker for clear-cell RCC. Our findings also reveal a new clinical significance of galectin-1 — that high proportions of galectin-1-expressing CD4+ and CD8+ lymphocytes were positively associated with poor clinicopathological features.

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Haupt, Sonja, Michele Tisdale, Michelle Vincendeau, Mary Anne Clements, David T. Gauthier, Raymond Lance, O. John Semmes et al. « Human endogenous retrovirus transcription profiles of the kidney and kidney-derived cell lines ». Journal of General Virology 92, n^o 10 (1 octobre 2011) : 2356–66. http://dx.doi.org/10.1099/vir.0.031518-0.

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The human genome comprises approximately 8–9 % of human endogenous retroviruses (HERVs) that are transcribed with tissue specificity. However, relatively few organs have been examined in detail for individual differences in HERV transcription pattern, nor have tissue-to-cell culture comparisons been frequently performed. Using an HERV-specific DNA microarray, a core HERV transcription profile was established for the human kidney comparing 10 tissue samples. This core represents HERV groups expressed uniformly or nearly so in non-tumour kidney tissue. The profiles obtained from non-tumour tissues were compared to 10 renal tumour tissues (renal cell carcinoma, RCC) derived from the same individuals and additionally, to 22 RCC cell lines. No RCC cell line or tumour-specific differences were observed, suggesting that HERV transcription is not altered in RCC. However, when comparing tissue transcription to cell line transcription, there were consistent differences. The differences were irrespective of cancer state and included cell lines derived from non-tumour kidney tissue, suggesting that a specific alteration of HERV transcription occurs when establishing cell lines. In contrast to previous publications, all known HERV-derived tumour antigens, including those identified in RCC, were expressed both in multiple RCC cell lines and several non-tumour tissue-derived cell lines, a result that contrasts with findings from patient samples. The results establish the core kidney transcription pattern of HERVs and reveal differences between cell culture lines and tissue samples.

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Ye, Xueting, Jing Xie, Hang Huang et Zhexian Deng. « Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells ». Cellular Physiology and Biochemistry 45, n^o 3 (2018) : 1205–18. http://dx.doi.org/10.1159/000487452.

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Background/Aims: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). Methods: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. Results: MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. Conclusion: MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling.

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Mohammed, Maisa Hashem, et Nagwa Abd El-Sadek Ahmed. « Significance of Immunohistochemical Expression of Survivin in Renal Cell Carcinoma ». Asian Pacific Journal of Cancer Biology 6, n^o 3 (12 août 2021) : 201–5. http://dx.doi.org/10.31557/apjcb.2021.6.3.201-205.

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Background: Evasion of apoptosis is an essential alteration for cellular genetic mutation. Survivin is a member of inhibitor of apoptosis protein (IAP) family. Under normal conditions, Survivin is expressed in embryonic and fetal tissues and markedly diminished in mature, differentiated adult tissues. Survivin was found to be re-expressed in multiple solid and hematological human malignant neoplasms. The purpose of this study was to evaluate the expression of Survivin in renal cell carcinoma (RCC), and to find statistically significant associations between Survivin and the tested Clinicopathological parameters.Methods: 39 patients with RCCs who underwent nephrectomy were included in the study. From each RCC specimen, two tissue sections were obtained; one was stained by H&E stain to determine both RCC phenotype and Fuhrman’s nuclear grades. The second tissue section was immunohistochemically stained by anti-human Survivin antibody. Results: The study revealed statistically significant associations between Survivin expression in RCC specimens and RCC histological types (p =0.002), high tumor grade (p< 0.001) and advanced tumor stage (p< 0.001). Conclusion: The study revealed that Survivin is positively correlated to poorly differentiated RCCs with high Fuhrman’s nuclear grade and advanced tumor stage.

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Park, Jee Soo, Myung Eun Lee, Won Sik Jang, Koon Ho Rha, Seung Hwan Lee, Jongsoo Lee et Won Sik Ham. « The DEAD/DEAH Box Helicase, DDX11, Is Essential for the Survival of Advanced Clear Cell Renal Cell Carcinoma and Is a Determinant of PARP Inhibitor Sensitivity ». Cancers 13, n^o 11 (24 mai 2021) : 2574. http://dx.doi.org/10.3390/cancers13112574.

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Genes associated with the DEAD-box helicase DDX11 are significant biomarkers of aggressive renal cell carcinoma (RCC), but their molecular function is poorly understood. We analyzed the molecular pathways through which DDX11 is involved in RCC cell survival and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Immunohistochemistry and immunoblotting determined DDX11 expression in normal kidney tissues, benign renal tumors, and RCC tissues and cell lines. Quantitative polymerase chain reaction validated the downregulation of DDX11 in response to transfection with DDX11-specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of DDX11 knockdown on RCC cells, and the relevant effects of sunitinib, olaparib, and sunitinib plus olaparib were evaluated. DDX11 was upregulated in high-grade, advanced RCC compared to low-grade, localized RCC, and DDX11 was not expressed in normal kidney tissues or benign renal tumors. DDX11 knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. DDX11-deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, DDX11 could determine PARP inhibitor sensitivity in RCC. DDX11 could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.

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Morais, Christudas, Retnagowri Rajandram, Jade S. Blakeney, Abishek Iyer, Jacky Y. Suen, David W. Johnson, Glenda C. Gobe, David P. Fairlie et David A. Vesey. « Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines ». PLOS ONE 16, n^o 3 (25 mars 2021) : e0248983. http://dx.doi.org/10.1371/journal.pone.0248983.

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Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.

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Jung, Maria, Jörg Ellinger, Heidrun Gevensleben, Isabella Syring, Christine Lüders, Luka de Vos, Svenja Pützer et al. « Cell-Free SHOX2 DNA Methylation in Blood as a Molecular Staging Parameter for Risk Stratification in Renal Cell Carcinoma Patients : A Prospective Observational Cohort Study ». Clinical Chemistry 65, n^o 4 (1 avril 2019) : 559–68. http://dx.doi.org/10.1373/clinchem.2018.297549.

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Abstract BACKGROUND Novel targeted treatments and immunotherapies have substantially changed therapeutic options for advanced and metastatic renal cell carcinomas (RCCs). However, accurate diagnostic tests for the identification of high-risk patients are urgently needed. Here, we analyzed SHOX2 mRNA expression in RCC tissues and SHOX2 gene body methylation quantitatively in circulating cell-free DNA (ccfDNA) and RCC tissues with regard to risk stratification. METHODS The clinical performance of SHOX2 methylation was tested retrospectively and prospectively in a training and testing cohort of RCC tissue samples (n = 760 in total). SHOX2 mRNA expression analysis was included in the training cohort. In matched blood plasma samples from the testing cohort (n = 100), we prospectively examined the capability of pretherapeutic quantitative SHOX2 ccfDNA methylation to assess disease stage and identify patients at high risk of death. RESULTS SHOX2 gene body methylation was positively correlated with mRNA expression in RCC tissues (training cohort: Spearman ρ = 0.23, P < 0.001). SHOX2 methylation in tissue and plasma strongly correlated with an advanced disease stage (training cohort: ρ = 0.28, P < 0.001; testing cohort/tissue: ρ = 0.40, P < 0.001; testing cohort/plasma: ρ = 0.34, P = 0.001) and risk of death after initial partial or radical nephrectomy [training cohort: hazard ratio (HR) = 1.40 (95% CI, 1.24–1.57), P < 0.001; testing cohort/tissue: HR = 1.16 (95% CI, 1.07–1.27), P = 0.001; testing cohort/plasma: HR = 1.50 (95% CI, 1.29–1.74), P < 0.001]. CONCLUSIONS Pretherapeutic SHOX2 ccfDNA methylation testing allows for the identification of RCC patients at high risk of death after nephrectomy. These patients might benefit from an adjuvant treatment or early initiation of a palliative treatment.

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Yao, Lv, Xiaoqiang Guo et Yaoting Gui. « Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression ». Cellular Physiology and Biochemistry 45, n^o 3 (2018) : 984–92. http://dx.doi.org/10.1159/000487293.

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Background/Aims: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results: Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion: These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC.

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Jirásko, Robert, Jakub Idkowiak, Denise Wolrab, Aleš Kvasnička, David Friedecký, Krzysztof Polański, Hana Študentová, Vladimír Študent, Bohuslav Melichar et Michal Holčapek. « Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma ». Cancers 14, n^o 19 (23 septembre 2022) : 4622. http://dx.doi.org/10.3390/cancers14194622.

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Purpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. Methods: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. Results: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844–0.954), while for urine samples it was 0.867 (0.763–0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832–0.952) and 0.981 (0.956–0.998), respectively. Conclusion: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models.

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Zhang, Xintao, Meng Zhang, Jianli Cheng, Zhaojie Lv, Feng Wang et Zhiming Cai. « MiR-411 Functions as a Tumor Suppressor in Renal Cell Cancer ». International Journal of Biological Markers 32, n^o 4 (octobre 2017) : 454–60. http://dx.doi.org/10.5301/ijbm.5000261.

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Background Recent studies have revealed that microRNAs (miRNAs) play important roles as oncogenes or tumor suppressors in tumorigenesis and tumor development, by negatively regulating protein expression. A previous study of microarrays identified that miR-411 was down-regulated in renal cell carcinoma (RCC), while few studies investigating the role of miR-411 in the pathogenesis of RCC have been performed. Methods We assessed the miR-411 expression in RCC and paired adjacent normal tissues, as well as in RCC cell lines and a normal renal cell line, by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Furthermore, the effects of miR-411 on RCC and normal renal cell proliferation, apoptosis and migration were determined using MTT assay, CCK-8 assay, flow cytometry and scratch wound assay following restoration of miR-411 with synthetic mimics. Results Results of qRT-PCR indicated that the expression of miR-411 was down-regulated in RCC tissues and cell lines when compared with adjacent normal tissues and a normal renal cell line. Further, results of CCK-8, MTT, cell scratch and transwell assay showed that over-expression of miR-411 suppressed RCC cell (786-0 and ACHN) proliferation and migration. Flow cytometry assay revealed that miR-411 could induce RCC cell apoptosis. However, overexpression of miR-411 had no obvious effect on normal renal cell line 293T Conclusions To sum up, miR-411 is significantly down-regulated and plays a role as a tumor suppressor in RCC. Further studies are warranted to determine the mechanisms of miR-411 in RCC pathogenesis and define the target genes of miR-411 in RCC.

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Xu, Xiangfei, et Dongsheng Zhu. « Prognostic significance of subclassifying stage pT3a renal tumors with fat invasion : a retrospective study of 99 patients ». Journal of International Medical Research 49, n^o 8 (août 2021) : 030006052110331. http://dx.doi.org/10.1177/03000605211033178.

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Purpose To analyze the recurrence in patients with clinic stage T1 renal cell carcinoma (RCC) who were upstaged to stage T3a after partial nephrectomy (PN) using a new sub-classification criterion. Methods A retrospective study of pathological characteristics was performed in patients who were upstaged to pT3a on the basis of fat invasion (FI). Results After analyzing the pathological findings, we proposed the following new sub-classification criteria for pT3a RCC with FI: (1) renal tumor invades the pseudo-capsule and contacts the perinephric adipose tissue directly or the tumor protrudes into the perinephric adipose tissue like a tongue (Type A); and (2) tumor nodules are distributed in perinephric adipose tissues (Type B). A significant difference was observed in the recurrence rate between the two subtypes A and B. For Type B, the recurrence rate after radical nephrectomy (RN) and PN was 15.79% and 63.64%, respectively. The recurrence rates for Types A and B after PN were 11.11% and 63.64%, respectively. Conclusions T3a RCC with tumor nodules in perinephric adipose and/or an irregular tumor protruding into the adipose tissues lead to a higher recurrence rate. We recommend that T3a RCC be carefully analyzed and patients be treated on an individual basis.

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Kowalewski, Adam, Damian Jaworski, Jędrzej Borowczak, Mateusz Maniewski, Krzysztof Szczerbowski, Paulina Antosik, Justyna Durślewicz et al. « TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma ». International Journal of Molecular Sciences 23, n^o 23 (25 novembre 2022) : 14702. http://dx.doi.org/10.3390/ijms232314702.

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Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.

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Oosterwijk, E., N. H. Bander, C. R. Divgi, S. Welt, J. C. Wakka, R. D. Finn, E. A. Carswell, S. M. Larson, S. O. Warnaar et G. J. Fleuren. « Antibody localization in human renal cell carcinoma : a phase I study of monoclonal antibody G250. » Journal of Clinical Oncology 11, n^o 4 (avril 1993) : 738–50. http://dx.doi.org/10.1200/jco.1993.11.4.738.

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PURPOSE To define the imaging and biodistribution characteristics of iodine 131-labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell-surface antigen expressed by human renal cell carcinoma (RCC). PATIENTS AND METHODS G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level. RESULTS Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250-negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250-positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%. CONCLUSION 131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential.

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Feng, Jia-fu, Wen-yu Yang, Yao-dong Wang, Gang Xie, Bei Xu, Chun-mei Dai, Bin Zhang, Xiao-han Li, Jun Wang et Yu-wei Yang. « Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of SLC39A14 ». Oxidative Medicine and Cellular Longevity 2022 (26 août 2022) : 1–17. http://dx.doi.org/10.1155/2022/8645830.

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Background. Covalently closed circular RNAs (circRNAs) play critical oncogenic or anticancer roles in various cancers including renal cell carcinoma (RCC), pointing to their regulation as a promising strategy against development of RCC. We, thus, studied the tumor-suppressive role of circ_000829 in RCC through in vitro and in vivo experiments. Methods. The expression of circ_000829 was validated in clinical RCC tissues and RCC cell lines. Based on ectopic expression and knockdown experiments, we examined the interactions among circ_000829, serine and arginine rich splicing factor 1 (SRSF1), and solute carrier family 39 member 14 (SLC39A14, zinc transporter). Then, the effects of circ_000829, SRSF1, and SLC39A14 on cell cycle distribution and proliferation in vitro and on tumor growth in vivo were evaluated in RCC cells. Results. Circ_000829 was poorly expressed in RCC tissues and cells, while SRSF1 was highly expressed. Restoration of circ_000829 reduced the levels of SRSF1 and SLC39A14B, thereby repressing the RCC cell proliferation in vitro and tumor growth in vivo. Meanwhile, overexpression of SRSF1 and SLC39A14B promoted the proliferation and cell cycle entry of RCC cells. Mechanistically, circ_000829 directly bound to SRSF1, and SRSF1 enhanced the expression of SLC39A14B by mediating the alternative splicing of SLC39A14. SLC39A14B upregulation negated the effect of SLC39A14 knockdown on RCC cell proliferation. Conclusion. Hence, this study suggests the antiproliferative role of circ_000829 in RCC growth and further elucidates the underlying mechanism involving the inhibited SRSF1-mediated alternative splicing of SLC39A14 mRNA.

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Abd El-Fadeal, Noha M. Abd, Alia Ellawindy, Mohammed A. Jeraiby, Safaa Y. Qusti, Eida M. Alshammari, Ahmad Khuzaim Alzahrani, Ezzat A. Ismail et al. « HSP70 Expression Signature in Renal Cell Carcinoma : A Clinical and Bioinformatic Analysis Approach ». Genes 14, n^o 2 (30 janvier 2023) : 355. http://dx.doi.org/10.3390/genes14020355.

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Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = −0.87, p < 0.001). Kaplan–Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

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Hour, Tzyh-Chyuan, Yi-Zih Kuo, Guang-Yaw Liu, Wang-Yi Kang, Chao-Yuan Huang, Yu-Chieh Tsai, Wen-Jeng Wu, Shu-Pin Huang et Yeong-Shiau Pu. « Downregulation of ABCD1 in Human Renal Cell Carcinoma ». International Journal of Biological Markers 24, n^o 3 (juillet 2009) : 171–78. http://dx.doi.org/10.1177/172460080902400307.

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Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Delayed diagnosis may result in progression and metastasis. Markers for early detection of RCC are lacking. The ATP-binding cassette transporter D1 (ABCD1) is located in the human peroxisome membrane. Its mutation causes X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder affecting lipid storage. The role of ABCD1 in human renal tumorigenesis was unclear. In this study, three pairs of RCC tissues were examined by cDNA microarray and data suggested that ABCD1 mRNA is downregulated. Downregulation of ABCD1 expression was confirmed by real-time PCR. ABCD1 expression was also downregulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. ABCD1 mRNA and protein expression levels assessed by immunohistochemistry in the RCC tissues were similar between genders, tumor grades, and tumor stages. Immunohisto-chemical assays also showed that ABCD1 expression was significantly higher in normal than in cancerous tissues (p<0.001). ABCD1 downregulation may be involved in human renal tumorigenesis.

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Xiao-fen, Wu, Chen Ting, Li Jie, Ma Deng-yang, Zhu Qing-feng et Lian Xin. « Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma ». Open Medicine 11, n^o 1 (1 janvier 2016) : 226–30. http://dx.doi.org/10.1515/med-2016-0043.

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AbstractObjectiveThe aim of this study was to investigate the correlation of von Hippel-Lindau tumor suppressor (VHL) mRNA expression and jade family PHD finger 1 (Jade-1) gene expression in patients with renal cell carcinoma (RCC). Another aim of this study was to analyze the relationship of these two genes with clinicalpathological features of the RCC patients. Methods: A total of 75 RCC patients who received surgically therapy in our hospital were included. All patients had complete pathological data. The expression of VHL/Jade-1 was determined by real-time polymerase chain reaction (RT-PCR). Results: VHL and Jade-1 were both obviously downregulated in RCC tissues than that of the matched normal tissues, and both negatively correlated with tumor size as well as tumor grade. And we found a fine association of VHL gene expression with Jade-1. Conclusion: VHL/Jade-1 exhibited significantly decreased expression in RCC tissues and was closely related to the clinical prognosis of patients. The finding of VHL expression positively correlated with Jade-1 expression shed light and provided crucial evidence on the connection of VHL protein with Wnt/b-catenin pathway.

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Gong, Aihong, Xinyu Zhao, Yue Pan, Yu Qi, Shuangda Li, Yiran Huang, Yanru Guo, Xia Qi, Wei Zheng et Li Jia. « The lncRNA MEG3 mediates renal cell cancer progression by regulating ST3Gal1 transcription and EGFR sialylation ». Journal of Cell Science 133, n^o 16 (31 juillet 2020) : jcs244020. http://dx.doi.org/10.1242/jcs.244020.

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ABSTRACTLong noncoding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Abnormal sialylation leads to renal cell carcinoma (RCC) malignancy. However, the mechanism by which the lncRNA maternally expressed gene 3 (MEG3) mediates RCC progression by regulating ST3Gal1 transcription and EGFR sialylation is still unrevealed. Here, we found that the expression of MEG3 was higher in adjacent tissues than in RCC tissues, as well as downregulated in RCC cell lines compared to expression in normal renal cells. The proliferation, migration and invasion of RCC cells transfected with MEG3 was decreased, whereas knockdown of MEG3 had the opposite effect. The proliferative and metastatic abilities of RCC cells in vivo were concordant with their behavior in vitro. ST3Gal1 expression was dysregulated in RCC and was positively correlated with MEG3. By applying bioinformatics, c-Jun (also known as JUN) was identified as a transcription factor predicted to bind the promoter of ST3Gal1, and altered MEG3 levels resulted in changes to c-Jun expression. Furthermore, ST3Gal1 modulated EGFR sialylation to inhibit EGFR phosphorylation, which affected activation of the phosphoinositide 3-kinase (PI3K)–AKT pathway. Taken together, our findings provide a novel mechanism to elucidate the role of the MEG3–ST3Gal1–EGFR axis in RCC progression.

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White, Nicole M. A., Olena Masui, Leroi DeSouza, Olga Krakovska, Ajay Matta, Georg A. Bjarnason, K. W. Michael Siu et George M. Yousef. « Relative quantification of protein expression in metastatic renal cell carcinoma using iTRAQ LC-MS/MS analysis reveals galectin-1 as a potential prognostic marker and therapeutic target. » Journal of Clinical Oncology 31, n^o 6_suppl (20 février 2013) : 412. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.412.

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412 Background: Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant cancers. Identification of proteins involved in tumor progression will help gain a better understanding of the disease and will form the basis for the identification of novel therapeutic targets. Methods: Using six fresh-frozen primary and six unmatched metastatic RCC tumors, we used iTRAQ labeling and LC-MS/MS analysis to identify proteins differentially expressed in metastatic versus primary RCC. We verified protein expression by western blot and immunohistochemical analyses and the measured the effect of dysregulated protein expression on biological processes with RCC cell line models. Results: After analysis, we identified 29 proteins differentially expressed in metastatic versus primary RCC. We verified expressions of profilin-1, 14-3-3 zeta/delta, and galectin-1 (Gal-1) on two independent tissue sets by western blot (10 primary and 10 metastatic RCC tissues) and immunohistochemistry (22 primary and 23 metastatic tissues). Overexpression of Gal-1 in CAKI-1 cells lead to decreased actin, increased vimentin expression, and increased cellular migration. Additionally, when Gal-1 was decreased via siRNA, cells showed decreased cellular migration. Protein array analysis showed expression of cell motility-related proteins HSP27, JNK, and RSK, were altered after siRNA transfection. We also showed that Gal-1 expression was increased in response to HIF-1alpha. Furthermore, we analyzed the expression of Gal-1 mRNA in 404 RCC patients using the Cancer Genome Anatomy Project, and found that patients who had higher Gal-1 expression in the primary RCC had significantly decreased overall survival (41 vs. 78 months; p < 0.01). Conclusions: Gal-1 is increased in metastatic RCC and can effect cell migration by targeting proteins involved in cell motility. This may be a downstream effect of HIF-1α dysregulation. Decreased Gal-1 significantly decreased cellular migration suggesting Gal-1 may serve as a potential therapeutic target. Additionally, we showed that increased Gal-1 expression was associated with decreased overall survival.

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Peters, Inga, Christel Reese, Natalia Dubrowinskaja, Wiebke Inga Antonopoulos, Martin Krause, Tu Nghi Dang, Alexander Grote et al. « DNA methylation signature for the assessment of metastatic risk in primary renal cell cancer. » Journal of Clinical Oncology 35, n^o 6_suppl (20 février 2017) : 516. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.516.

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516 Background: Transition from localized renal cell cancer (RCC) to metastatic disease is associated with an immense mortality. Beside clinicopathological risk estimation, a molecular prediction of metastatic risk from primary cancers with a sufficient diagnostic accuracy is not available. We biometrically identified a candidate metastasis associated methylation signature (MAMS) in a genome-wide in silico DNA methylation analysis of TCGA data and carried out a double evaluation study using tissues from localized RCC, primary metastatic RCC, and distant metastases. Methods: Candidate MAMS was identified by genome-wide random forest analyses of TCGA methylation level 3 data aiming for classification of 230 primary RCC without distant metastases and 52 metastasized tumors. Forty-nine pyrosequencing and/or quantitative methylation specific PCR analyses were established for a total of 20 candidate methylated loci. For evaluation of MAMS, DNA was isolated and bisulfite converted from the primary RCC tissue cohort (n=187) as well as 99 distant metastases. Localized RCCs consisted of 92 pT1a/b tumors (clear cell, 73; papillary, 16; chromophobe, 2; not classified, 1) without lymph node or distant metastases. RCC samples of primary metastatic disease were obtained from 31 patients. Results: Single candidate loci showed specific hypermethylation when metastatic tissues were compared to primary RCC samples. Random forest analysis showed that MAMS including nine methylation loci achieved a sensitivity of 93% and a specificity of 89% (AUC 0.95) for differentiation of localized RCC and metastases (chi square, p = 3.4*10-29). Positive, negative likelihood, and diagnostic odds ratios were 8.6, 0.08, and 108. Using this random forest model for prediction of primary RCCs associated with distant or lymph node metastases revealed a sensitivity of 58% and specificity of 94% (AUC 0.84, p = 1.0*10-9). Positive, negative likelihood, and diagnostic odds ratios were 9.2, 0.45, and 20.5. Conclusions: A negative MAMS test result retrospectively reduced the probability of metastasis 15-fold in the localized disease cohort, suggesting a prospective evaluation for a possible clinical translation of MAMS in handling RCC patients.

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Chang, Chi-Fen, Shu-Pin Huang, Yu-Mei Hsueh, Jiun-Hung Geng, Chao-Yuan Huang et Bo-Ying Bao. « Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression ». International Journal of Environmental Research and Public Health 19, n^o 19 (30 septembre 2022) : 12471. http://dx.doi.org/10.3390/ijerph191912471.

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SH3 and multiple ankyrin repeat domains (SHANK) is a family of scaffold proteins that were first identified to be involved in balancing synaptic transmission via regulation of intracellular signalling crosstalk and have been linked to various cancers. However, the role of the SHANK genes in renal cell carcinoma (RCC) remains to be elucidated. In this study, we aimed to evaluate whether genetic variants in SHANK family genes affect the risk of RCC and survival of patients. A genetic association study was conducted using logistic regression and Cox regression analyses, followed by the correction for a false discovery rate (FDR), in 630 patients with RCC and controls. A pooled analysis was further performed to summarise the clinical relevance of SHANK gene expression in RCC. After adjustment for known risk factors and the FDR, the SHANK2 rs10792565 T allele was found to be associated with an increased risk of RCC (adjusted odds ratio = 1.79, 95% confidence interval = 1.32–2.44, p = 1.96 × 10−4, q = 0.030), whereas no significant association was found with RCC survival. A pooled analysis of 19 independent studies, comprising 1509 RCC and 414 adjacent normal tissues, showed that the expression of SHANK2 was significantly lower in RCC than in normal tissues (p < 0.001). Furthermore, low expression of SHANK2 was correlated with an advanced stage and poor prognosis for patients with clear cell and papillary RCC. This study suggests that SHANK2 rs10792565 is associated with an increased risk of RCC and that SHANK2 may play a role in RCC progression.

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Oh, Euiyoung, Jun-Hyeong Kim, JungIn Um, Da-Woon Jung, Darren R. Williams et Hyunju Lee. « Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma ». Cancers 13, n^o 12 (18 juin 2021) : 3045. http://dx.doi.org/10.3390/cancers13123045.

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The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.

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Su, Yaowu, Liang Zhou, Qin Yu, Jianjun Lu et Wei Liu. « Long Non-Coding RNA LOC648987 Promotes Proliferation and Metastasis of Renal Cell Carcinoma by Regulating Epithelial-Mesenchymal Transition ». Technology in Cancer Research & ; Treatment 20 (1 janvier 2021) : 153303382199783. http://dx.doi.org/10.1177/1533033821997834.

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Renal cell carcinoma (RCC) is a type of urinary tumor with a high incidence and is often associated with tumor metastasis. Long non-coding RNA (lncRNA) regulates tumorigenesis, progression, and metastasis. However, the role and the predictive value of lncRNA in RCC progression and metastasis have not been elucidated. The purpose of this study was to evaluate the effect of a newly discovered lncRNA LOC648987 on RCC proliferation and metastasis. LOC648987 was identified by RT-PCR for high expression in human RCC tissues as well as in metastatic RCC tissues. In the cell experiments, we infected the RCC cell lines ACHN and 786-O cells with LOC648987-shRNA and its negative control (shNC). The results showed that the knockdown of LOC648987 inhibited the proliferation of ACHN and 786-O cells and colony formation. The cell cycle and the apoptosis progression of ACHN and 786-O cells were assessed using flow cytometry. The knockdown of LOC648987 significantly inhibited the progression of ACHN and 786-O cells from G0/G1 to S phase and promoted cell apoptosis. The metastasis promoting effects of LOC648987 on ACHN and 786-O cells were verified by transwell migration assays, which depended on vimentin and MMP-9 to regulate the epithelial–mesenchymal transition. Finally, the promotion of LOC648987 on RCC tumorigenesis was evaluated in BALb/c nude mice. These data confirmed that lncRNA LOC648987 promoted RCC cell proliferation and tumor metastasis and regulated the expression of EMT-related proteins in RCC cells.

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Mizutani, Yoichi, Hiroyuki Nakanishi, Kosuke Yamamoto, Yong Nan Li, Hiroki Matsubara, Kazuya Mikami, Koji Okihara, Akihiro Kawauchi, Benjamin Bonavida et Tsuneharu Miki. « Downregulation of Smac/DIABLO Expression in Renal Cell Carcinoma and Its Prognostic Significance ». Journal of Clinical Oncology 23, n^o 3 (20 janvier 2005) : 448–54. http://dx.doi.org/10.1200/jco.2005.02.191.

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Purpose Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers, including renal cell carcinoma (RCC). This study examined Smac/DIABLO expression in 78 healthy kidneys and 78 RCCs. Materials and Methods The level of Smac/DIABLO expression was quantified by Western blot analysis using nonfixed fresh frozen tissues. Results The expression of Smac/DIABLO was lower in RCC compared with the autologous normal kidney. Sixty-four (82%) of 78 of RCC expressed Smac/DIABLO, and 18% were negative, whereas 100% of normal kidney tissues were positive. In stage I/II RCC, 96% expressed Smac/DIABLO, whereas only 50% expressed Smac/DIABLO in stage III/IV. Smac/DIABLO expression inversely correlated with the grade of RCC. Patients with RCC expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression in the 5-year follow-up. Transfection with Smac/DIABLO cDNA enhanced tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) –mediated and cisplatin-mediated cytotoxicity in RCC. Conclusion The present study demonstrates for the first time that Smac/DIABLO expression was downregulated in RCC and that no Smac/DIABLO expression in RCC predicted a worse prognosis. In addition, transfection with Smac/DIABLO sensitized RCC to TRAIL/cisplatin-induced apoptosis. These results suggest that Smac/DIABLO expression in RCC may be used as a prognostic parameter, and that enhancement of Smac/DIABLO expression in RCC may potentiate immunotherapy and chemotherapy.

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Zhiqiang, Wang, Liu Qian, Li Tieqiang, Li Xiaodong, Zhang Guangwei, Li Yang, Zi Hao et Zhu Chaoyang. « Abnormal expressed long non-coding RNA IRAIN inhibits tumor progression in human renal cell carcinoma cells ». Open Life Sciences 11, n^o 1 (1 janvier 2016) : 200–205. http://dx.doi.org/10.1515/biol-2016-0026.

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AbstractObjectivesThe long non-coding RNA (lncRNA) IRAIN has been verified to have key roles in tumor biology. The aim of this study was to explore its expression and biological functions in human renal cell carcinoma (RCC) cells.MethodsQuantitative RT-PCR was applied to detect the RNA expression of IRAIN in RCC tissues and cell lines when compared with respective controls. MTT and flow cytometry methods were respectively used to monitor the cell proliferation and apoptosis of 786-O cells after IRAIN was overexpressed. Altered expression of cyclin D1 and Bax was determined by immunoblotting. Xenograft models were finally carried out to confirm the roles of IRAIN in RCC in vivo.ResultsIRAIN expression was found to be remarkably decreased in RCC tissues and cell lines. Its overexpression in 786-O cells significantly inhibited cell proliferation and promoted apoptosis. We further demonstrated that cyclin D1 was reduced while apoptosis promoting protein Bax was elevated in IRAIN-overexpressed 786-O cells. Importantly, we found that IRAIN overexpression could suppress in vivo tumorigenesis of RCC, reflected by tumor volume and tumor weight measurement.ConclusionIRAIN might serve as a novel tumor suppressing lncRNA and a potential therapeutic target in RCC treatment.

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Miranda-Gonçalves, Vera, Ana Lameirinhas, Catarina Macedo-Silva, João Lobo, Paula C. Dias, Verónica Ferreira, Rui Henrique et Carmen Jerónimo. « Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation ». Cells 9, n^o 4 (23 avril 2020) : 1053. http://dx.doi.org/10.3390/cells9041053.

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Background: Renal cell carcinoma (RCC) displays a glycolytic phenotype (Warburg effect). Increased lactate production, impacting on tumor biology and microenvironment modulation, has been implicated in epigenetic mechanisms’ regulation, leading to histone deacetylases inhibition. Thus, in-depth knowledge of lactate’s impact on epigenome regulation of highly glycolytic tumors might allow for new therapeutic strategies. Herein, we investigated how extracellular lactate affected sirtuin 1 activity, a class III histone deacetylase (sirtuins, SIRTs) in RCC. Methods: In vitro and in vivo interactions between lactate and SIRT1 in RCC were investigated in normal kidney and RCC cell lines. Finally, SIRT1 and N-cadherin immunoexpression was assessed in human RCC and normal renal tissues. Results: Lactate inhibited SIRT1 expression in normal kidney and RCC cells, increasing global H3 and H3K9 acetylation. Cells exposed to lactate showed increased cell migration and invasion entailing a mesenchymal phenotype. Treatment with a SIRT1 inhibitor, nicotinamide (NAM), paralleled lactate effects, promoting cell aggressiveness. In contrast, alpha-cyano-4-hydroxycinnamate (CHC), a lactate transporter inhibitor, reversed them by blocking lactate transport. In vivo (chick chorioallantoic membrane (CAM) assay), lactate and NAM exposure were associated with increased tumor size and blood vessel recruitment, whereas CHC displayed the opposite effect. Moreover, primary RCC revealed N-cadherin upregulation whereas SIRT1 expression levels were downregulated compared to normal tissues. Conclusions: In RCC, lactate enhanced aggressiveness and modulated normal kidney cell phenotype, in part through downregulation of SIRT1, unveiling tumor metabolism as a promising therapeutic target.

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Zhong, Weifeng, Zhiming Wu, Nanhui Chen, Kaihua Zhong, Yifeng Lin, Huiming Jiang, Pei Wan, Shanming Lu, Lawei Yang et Siping Liu. « Eupatilin Inhibits Renal Cancer Growth by Downregulating MicroRNA-21 through the Activation of YAP1 ». BioMed Research International 2019 (24 avril 2019) : 1–11. http://dx.doi.org/10.1155/2019/5016483.

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Renal cell carcinoma (RCC) is the second most common human urinary tumor. Eupatilin is the main active ingredient of the traditional Chinese medicineArtemisia asiatica. The effect of Eupatilin on RCC and the underlying mechanism remain unknown. Here, we investigated the anticancer effects and mechanisms of Eupatilin in RCCin vivoandin vitro, laying an experimental foundation for the clinical application of Eupatilin in the treatment of RCC. The results showed that Eupatilin significantly inhibited 786-O cell viability and migration and promoted apoptosis. Eupatilin inhibited the expression of miR-21 in 786-O cells, and overexpression of miR-21 suppressed the effect of Eupatilin on viability, apoptosis, and migration in 786-O cells. Eupatilin inhibited the growth of renal tumors in nude mice by downregulating miR-21. YAP1, which was identified as a target of miR-21, showed significantly lower expression in RCC tissues than in healthy tissues. miR-21 significantly inhibited YAP1 protein expression in 786-O cells and tumor tissues isolated from nude mice, and YAP1 attenuated the effect of miR-21 on the viability, apoptosis, and migration of 786-O cells. In conclusion, Eupatilin inhibited the expression of miR-21, which mediated the proapoptotic and antimigratory effects of Eupatilin by suppressing YAP1 in renal cancer cells. These results suggested that Eupatilin could be a potent agent for the treatment of RCC.

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Cherkasova, Elena, Elizabeth Malinzak, Sheila Rao, Vera N. Senchenko, Anna V. Kudryavtseva, Lev L. Kiselev, Yoshiyuki Takahashi et al. « Loss of Function of the VHL Tumor Suppressor Gene Resurrects An Endogenous Retrovirus in Kidney Cancer That Encodes a Tumor Antigen Targeted by Allogeneic T-Cells Following Hematopoietic Cell Transplantation (HCT). » Blood 114, n^o 22 (20 novembre 2009) : 467. http://dx.doi.org/10.1182/blood.v114.22.467.467.

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Abstract Abstract 467 Renal cell carcinoma (RCC) has recently been identified as a target for a graft-vs-tumor (GVT) effect following allogeneic hematopoietic cell transplantation (HCT). At the NHLBI, 30 of 76 patients (39%) with metastatic RCC were observed to have delayed tumor regression following a reduced intensity allogeneic HCT consistent with a GVT effect. A better understanding of the tumor antigens targeted by donor immune cells could lead to the development of transplant approaches that enhance GVT effects while avoiding GVHD. We detected RCC-reactive CD8+ T-cells by ELISPOT analysis in the blood of several responding patients with metastatic RCC following HCT that were absent before transplantation. Using PBMC obtained from a patient who had a graft-vs-RCC effect associated with prolonged disease free survival, we isolated CD8+ T-cell clones with RCC-specific tumor cytotoxicity. Utilizing cDNA expression cloning, we identified a 10 amino acid peptide to be the target antigen of RCC-specific T-cells. The genes encoding this antigen were found to be derived from a human endogenous retrovirus type E (named CT-RCC HERV-E) previously unknown to be expressed in any human tissues. Remarkably, RT-PCR showed this endogenous RV was expressed in the majority (13/17) of clear cell tumors but was not expressed in normal kidney tissues, or the non-clear cell histological subtypes of kidney cancer (0/16). A number of different endogenous retroviruses have recently been shown to be expressed in both solid tumors and hematological malignancies and can induce cytotoxic T-cell responses in vivo. However, the factors regulating transcriptional activity of most endogenous retrovirus that lead to tumor-restricted expression are poorly understood. Because the clear-cell histological subtype of RCC is characterized by inactivation of the VHL tumor-suppressor, we hypothesized VHL might regulate expression of CT-RCC HERV-E. RT-PCR showed VHL expression was absent in all clear cell tumors expressing the CT-RCC HERV-E. The HERV-E 5' LTR has a promoter with HIF response elements (HRE) that were found by bisulfite PCR sequencing to be extensively methylated in all normal tissues and non-clear cell RCC tumors but de-methylated in all HERV-E expressing clear cell kidney tumors. Transfection of wild type VHL into VHL mutated clear cell carcinomas dramatically reduced expression of HERV-E derived transcripts. In VHL mutant RCC cells, HIF-2α over-expression was required but alone was insufficient to induce HERV-E expression; SiRNA inhibition of HIF-2α silenced HERV-E expression, although the provirus was only expressed in clear cell tumors that expressed HIF-2α and had de-methylated proviral HREs. Conclusion: These data suggest loss of function of the VHL tumor suppressor leads to selective expression of an endogenous retrovirus in kidney cancer that serves as an antigenic target of T-cells in vivo. Because CT-RCC HERV-E is not expressed in normal tissues, antigens derived from this provirus could serve as excellent targets for cellular immunity. Disclosures: No relevant conflicts of interest to declare.

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Pontrelli, Paola, Margherita Gigante, Federica Spadaccino, Giuseppe Stefano Netti, Marilisa Saldarelli, Luigi Balducci, Maddalena Gigante et al. « CD40 Cross-Linking Induces Migration of Renal Tumor Cell through Nuclear Factor of Activated T Cells (NFAT) Activation ». International Journal of Molecular Sciences 22, n^o 16 (18 août 2021) : 8871. http://dx.doi.org/10.3390/ijms22168871.

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CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC.

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Rudzinska-Radecka, Magdalena, Anastasia S. Frolova, Anastasia V. Balakireva, Neonila V. Gorokhovets, Vadim S. Pokrovsky, Darina V. Sokolova, Dmitry O. Korolev et al. « In Silico, In Vitro, and Clinical Investigations of Cathepsin B and Stefin A mRNA Expression and a Correlation Analysis in Kidney Cancer ». Cells 11, n^o 9 (25 avril 2022) : 1455. http://dx.doi.org/10.3390/cells11091455.

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The cysteine protease Cathepsin B (CtsB) plays a critical role in multiple signaling pathways, intracellular protein degradation, and processing. Endogenous inhibitors regulate its enzymatic activity, including stefins and other cystatins. Recent data proved that CtsB is implicated in tumor extracellular matrix remodeling, cell invasion, and metastasis: a misbalance between cathepsins and their natural inhibitors is often considered a sign of disease progression. In the present study, we investigated CtsB and stefin A (StfA) expression in renal cell carcinoma (RCC). mRNA analysis unveiled a significant CTSB and STFA increase in RCC tissues compared to adjacent non-cancerogenic tissues and a higher CtsB expression in malignant tumors than in benign renal neoplasms. Further analysis highlighted a positive correlation between CtsB and StfA expression as a function of patient sex, age, tumor size, grade, lymph node invasion, metastasis occurrence, and survival. Alternative overexpression and silencing of CtsB and StfA confirmed the correlation expression between these proteins in human RCC-derived cells through protein analysis and fluorescent microscopy. Finally, the ectopic expression of CtsB and StfA increased RCC cell proliferation. Our data strongly indicated that CtsB and StfA expression play an important role in RCC development by mutually stimulating their expression in RCC progression.

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Rudzinska-Radecka, Magdalena, Anastasia S. Frolova, Anastasia V. Balakireva, Neonila V. Gorokhovets, Vadim S. Pokrovsky, Darina V. Sokolova, Dmitry O. Korolev et al. « In Silico, In Vitro, and Clinical Investigations of Cathepsin B and Stefin A mRNA Expression and a Correlation Analysis in Kidney Cancer ». Cells 11, n^o 9 (25 avril 2022) : 1455. http://dx.doi.org/10.3390/cells11091455.

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The cysteine protease Cathepsin B (CtsB) plays a critical role in multiple signaling pathways, intracellular protein degradation, and processing. Endogenous inhibitors regulate its enzymatic activity, including stefins and other cystatins. Recent data proved that CtsB is implicated in tumor extracellular matrix remodeling, cell invasion, and metastasis: a misbalance between cathepsins and their natural inhibitors is often considered a sign of disease progression. In the present study, we investigated CtsB and stefin A (StfA) expression in renal cell carcinoma (RCC). mRNA analysis unveiled a significant CTSB and STFA increase in RCC tissues compared to adjacent non-cancerogenic tissues and a higher CtsB expression in malignant tumors than in benign renal neoplasms. Further analysis highlighted a positive correlation between CtsB and StfA expression as a function of patient sex, age, tumor size, grade, lymph node invasion, metastasis occurrence, and survival. Alternative overexpression and silencing of CtsB and StfA confirmed the correlation expression between these proteins in human RCC-derived cells through protein analysis and fluorescent microscopy. Finally, the ectopic expression of CtsB and StfA increased RCC cell proliferation. Our data strongly indicated that CtsB and StfA expression play an important role in RCC development by mutually stimulating their expression in RCC progression.

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Rudzinska-Radecka, Magdalena, Anastasia S. Frolova, Anastasia V. Balakireva, Neonila V. Gorokhovets, Vadim S. Pokrovsky, Darina V. Sokolova, Dmitry O. Korolev et al. « In Silico, In Vitro, and Clinical Investigations of Cathepsin B and Stefin A mRNA Expression and a Correlation Analysis in Kidney Cancer ». Cells 11, n^o 9 (25 avril 2022) : 1455. http://dx.doi.org/10.3390/cells11091455.

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The cysteine protease Cathepsin B (CtsB) plays a critical role in multiple signaling pathways, intracellular protein degradation, and processing. Endogenous inhibitors regulate its enzymatic activity, including stefins and other cystatins. Recent data proved that CtsB is implicated in tumor extracellular matrix remodeling, cell invasion, and metastasis: a misbalance between cathepsins and their natural inhibitors is often considered a sign of disease progression. In the present study, we investigated CtsB and stefin A (StfA) expression in renal cell carcinoma (RCC). mRNA analysis unveiled a significant CTSB and STFA increase in RCC tissues compared to adjacent non-cancerogenic tissues and a higher CtsB expression in malignant tumors than in benign renal neoplasms. Further analysis highlighted a positive correlation between CtsB and StfA expression as a function of patient sex, age, tumor size, grade, lymph node invasion, metastasis occurrence, and survival. Alternative overexpression and silencing of CtsB and StfA confirmed the correlation expression between these proteins in human RCC-derived cells through protein analysis and fluorescent microscopy. Finally, the ectopic expression of CtsB and StfA increased RCC cell proliferation. Our data strongly indicated that CtsB and StfA expression play an important role in RCC development by mutually stimulating their expression in RCC progression.

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Zeng, Jiawei, Yuanmeng Li, Yaodong Wang, Gang Xie, Qian Feng, Yuwei Yang et Jiafu Feng. « lncRNA 00312 Attenuates Cell Proliferation and Invasion and Promotes Apoptosis in Renal Cell Carcinoma via miR-34a-5p/ASS1 Axis ». Oxidative Medicine and Cellular Longevity 2020 (27 mars 2020) : 1–16. http://dx.doi.org/10.1155/2020/5737289.

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Background. Previous studies have demonstrated that lncRNAs play functional roles in regulating cancer cell proliferation, invasion, and apoptosis. Recent studies confirmed that lncRNA 00312 has important biological functions in lung and colorectal cancer. However, the role of lncRNA 00312 in renal cell carcinoma (RCC) remains unclear. Our aim was to explore the function of lncRNA 00312 in RCC and its potential molecular mechanism. Methods. RCC cell lines A498 and ACHN were used as in vitro models in this study. RT-PCR was performed to determine lncRNA 00312, miR-34a-5p, and ASS1 mRNA expression. Proliferation and invasion were examined by CCK-8 and Transwell assay to confirm the function role of lncRNA 00312. Western blot analysis was used to examine the expression of apoptotic proteins Bax and Bcl-2. Results. lncRNA was significantly downregulated in RCC cells such as A498 and ACHN; the expression of lncRNA 00312 in RCC tissues was significantly lower than that in adjacent normal tissues. Patients with low expression of lncRNA 00312 have worse prognosis regarding pathological grade, tumor size, and TNM stage. Overexpression of lncRNA 00312 suppressed A498 and ACHN cell proliferation and invasion, while promoting apoptosis. Our study found that miR-34a-5p had the potential binding site with lncRNA 00312 and revealed the role of miR-34a-5p in RCC. Furthermore, we confirmed that lncRNA 00312 played its role with the participation of ASS1 and miR-34a-5p. Conclusion. lncRNA 00312 can inhibit RCC proliferation and invasion and promote apoptosis in vitro by suppressing miR-34a-5p and overexpressing ASS1. Our study demonstrated that the lncRNA 00312/miR-34a-5p/ASS1 axis may play a functional role in the progression of RCC; lncRNA 00312 abundance is a prognostic factor candidate for RCC survival, which provides new insights for RCC clinical treatment.

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Zhang, Xiaoting, Huaning Kang, Jing Xiao, Benyan Shi, Xiaofeng Li et Guihong Chen. « LHPP Inhibits the Proliferation and Metastasis of Renal Cell Carcinoma ». BioMed Research International 2020 (22 décembre 2020) : 1–9. http://dx.doi.org/10.1155/2020/7020924.

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Renal cell carcinoma (RCC) is one of the ten most common cancers in the globe. Despite the diagnosis and treatment of renal cell carcinoma that have made great improvements, the morbidity and mortality rates of renal cell carcinoma remain unchanged remarkably. LHPP is a kind of histidine phosphatases, acting as a tumor suppressor in the progression of various cancers. In this study, we found that LHPP was significantly downregulated in RCC tissues and cell lines. Decreased expression of LHPP was closely correlated with tumor size and postoperative metastasis of RCC patients. In addition, overexpression of LHPP inhibited the proliferation and metastasis of RCC. However, suppression of LHPP promoted the proliferation and metastasis of RCC. In conclusion, our results presented the important role of LHPP in the development and progression of RCC.

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Jin, Xue-fei, Hai Li, Shi Zong et Hong-yan Li. « Knockdown of Collagen Triple Helix Repeat Containing-1 Inhibits the Proliferation and Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma Cells ». Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 24, n^o 6 (27 octobre 2016) : 477–85. http://dx.doi.org/10.3727/096504016x14685034103716.

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Collagen triple helix repeat containing-1 (CTHRC1), a secreted glycoprotein, is frequently upregulated in human cancers. However, the functional role of CTHRC1 in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to explore the role of CTHRC1 in RCC. Our results demonstrated that CTHRC1 was upregulated in RCC tissues and cell lines. Knockdown of CTHRC1 significantly inhibits the proliferation in RCCs. Furthermore, knockdown of CTHRC1 significantly inhibited the epithelial-to-mesenchymal transition (EMT) process in RCCs, as well as suppressed RCC cell migration and invasion. Mechanistically, knockdown of CTHRC1 inhibited the expression of β-catenin, c-Myc, and cyclin D1 in RCC cells. In conclusion, the results of the present study indicated that CTHRC1 downregulation inhibited proliferation, migration, EMT, and β-catenin expression in RCC cells. Therefore, CTHRC1 may be a potential therapeutic target for the treatment of RCC.

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Marra, Caterina, Luigi Losco, Alessandra Ceccaroni, Paola Pentangelo, Donato Troisi et Carmine Alfano. « Metastatic Renal Cell Carcinoma to the Soft Tissue 27 Years after Radical Nephrectomy : A Case Report ». Medicina 59, n^o 1 (12 janvier 2023) : 150. http://dx.doi.org/10.3390/medicina59010150.

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Background and Objectives: Approximately 20–40% of patients affected with renal cell carcinoma (RCC) develop either distant metastatic or locally recurring disease following radical nephrectomy. Soft tissue, skin, and the central nervous system are less common metastatic sites. We present the case of a patient who has received a diagnosis of RCC; it was found that she had no metastases at the time of nephrectomy but had metastases in the soft tissue and subcutaneous tissue of the scalp 27 years later. As far as we can tell, this is the longest period elapsed between primary renal tumor and subcutaneous/soft tissue metastasis; moreover, this case is the first report of a combined soft tissue/subcutaneous metastasis from RCC. Case presentation: A 73-year-old woman underwent right radical nephrectomy 27 years earlier for clear cell renal cell carcinoma (CCRCC). She presented at our unit because she noticed swelling in the left temporal region; after radiological exams, a benign lesion was suspected. The patient underwent surgical eradication, but the massive bleeding did not allow the removal of the lesion. A biopsy of the mass was performed and the histological examination was consistent with RCC metastases. Conclusions: Metastases from renal cell carcinoma to the subcutaneous and soft tissues are rare. It is essential to take into account RCC metastases in the differential diagnostic of the new starting mass of the head and neck, and the necessity for close and continuous surveillance of patients diagnosed with renal cancer even after a long disease-free period should be emphasized.

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Qian, Yiguan, Yang Li, Luwei Xu, Ke Chen, Ning Liu, Xiaobing Yang, Qian Lv et al. « Tumor Cell-Derived Exosomal circ-PRKCI Promotes Proliferation of Renal Cell Carcinoma via Regulating miR-545-3p/CCND1 Axis ». Cancers 15, n^o 1 (25 décembre 2022) : 123. http://dx.doi.org/10.3390/cancers15010123.

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Renal cell carcinoma (RCC) originates from the epithelial cells of the renal tubules and has a high degree of malignancy and heterogeneity. Recent studies have found that exosomes regulate intercellular communication via transferring various bioactive molecules, such as circular RNAs (circRNAs), which are critical for cancer progression. However, the role of tumor cell-derived exosomal circRNAs in RCC remains unclear. In this study, we reported the high expression of circ-PRKCI in RCC tissues and serum exosomes. We also found that circ-PRKCI could be transferred exosomally from highly malignant RCC cells to relatively less malignant RCC cells. Tumor cell-derived exosomal circ-PRKCI promoted the proliferation, migration, and invasion of RCC cells, while inhibiting their apoptosis. Mechanistically, we found that circ-PRKCI promoted the proliferation of RCC via the miR-545-3p/CCND1 signaling pathway. Our study is the first to report the potential mechanisms of tumor cell-derived exosomal circ-PRKCI in RCC. In conclusion, this study will provide a new understanding about the molecular mechanisms of RCC progression.

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Paule, Bernard, Emmanuelle Deslandes, Stéphane E. Le Mouel, Laurence Bastien, Marie-Pierre Podgorniak, Yves Allory, Alexandre de la Taille, Suzanne Menashi, Fabien Calvo et Samia Mourah. « Identification of a Novel Biomarker Signature Associated with Risk for Bone Metastasis in Patients with Renal Cell Carcinoma ». International Journal of Biological Markers 25, n^o 2 (avril 2010) : 112–15. http://dx.doi.org/10.1177/172460081002500209.

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When renal cell carcinoma (RCC) metastasizes to bone (a frequent site of systemic spread of this cancer) it becomes highly resistant to radiation therapy and chemotherapy. A better understanding of the biology of bone metastasis in RCC may permit to identify biomarkers for early detection of subclinical disease and better stratification of patients prior to treatment. We therefore investigated in this study, using a multiplex real-time RT-PCR assay, the expression of a panel of 16 biomarkers involved in angiogenesis and tumor invasion; the panel was applied to primary tumors and normal tissues obtained from clear-cell RCC patients with and without bone metastases. We identified a novel combination of biomarkers associated with the risk of bone metastasis. Among the transcripts of the genes studied, VEGFR-1, VEGFR-2, HIF-1α, uPA, and PAI-1 overexpression in tumor tissues was significantly associated with the presence of bone metastasis (p=0.02, p=0.02, p<0.0001, p=0.04, and p=0.03, respectively). No differences were found in the expression of these transcripts in the corresponding normal tissues. This preliminary study provides a promising tool that may help in the management of RCC patients with bone metastasis. Indeed, these predictive markers could be useful to identify subclinical disease, improve staging, and guide treatment decisions.

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Kotecha, Ritesh, Erika Gedvilaite, Samuel J. Murray, Ashley Foster, Robert J. Motzer, Dana Tsui et Martin H. Voss. « Comparative circulating tumor DNA (ctDNA) genomic profiling in 110 patients with advanced renal cell carcinoma. » Journal of Clinical Oncology 38, n^o 6_suppl (20 février 2020) : 743. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.743.

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743 Background: Circulating tumor DNA (ctDNA) profiling is a non-invasive method to genomically assess solid tumors. Key benchmarks are required to assess applications in RCC management. To evaluate this tool broadly, we performed a large cohort analysis using a comparative approach to correlate clinical characteristics and matched oncogenomics of primary tumor and ctDNA. Methods: Pts with prior NGS sequenced mutational profiles from tumor (nephrectomy or metastatic tissues) underwent a single-time point plasma collection for ctDNA extraction. ctDNA targeted NGS sequencing was performed using MSK-IMPACT, with bi-directional cross genotype comparison using Waltz 2.0. Liberal (1-2 reads) and stringent (≥3 reads) filters were applied, with a cut-off of <30% allele frequency to remove germline alterations. Relevant clinical parameters were analyzed for correlation with ctDNA alteration frequency and load. Results: 110 metastatic clear-cell RCC pts, of whom available IMDC-risk was favorable (25%), intermediate (45%), or poor (4%) were included. 96% of pts had a nephrectomy prior to ctDNA collection, and most were heavily pre-treated (mean: 3 therapies, R: 0-8). The median time from diagnosis to ctDNA collection was 22.1 months (R: 2.3-215), and the median time from site specific tissue sequencing was 23.8 months (R: 1-177). 587 alterations were identified across the entire cohort in primary tissues, and 65% of pts had ≥1 alteration in ctDNA by liberal criteria. Detection rates for VHL and PBRM1 alterations were different in primary tissue and ctDNA (both liberal and stringent) with VHL altered in 92%, 43% and 50%, respectively; and PBRM1 altered in 50%, 25%, 21%, respectively. Conclusions: This large cohort analysis shows comparable mutational profiles of RCC-specific alterations in primary tissue and ctDNA, and highlights challenges of liquid biopsy approaches in RCC. Future efforts to correlate clinical outcomes with algorithm-based metrics will enhance the utility of this tool.[Table: see text]

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Holcakova, J., L. Hernychova, P. Bouchal, K. Brozkova, J. Zaloudik, D. Valik, R. Nenutil et B. Vojtesek. « Identification of αB-Crystallin, a Biomarker of Renal Cell Carcinoma by SELDI-TOF MS ». International Journal of Biological Markers 23, n^o 1 (janvier 2008) : 48–53. http://dx.doi.org/10.1177/172460080802300108.

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Spectrometric-based surface-enhanced laser desorption/ionization ProteinChip (SELDI-TOF) facilitates rapid and easy analysis of protein mixtures and is often exploited to define potential diagnostic markers from sera. However, SELDI-TOF is a relatively insensitive technique and unable to detect circulating proteins at low levels even if they are differentially expressed in cancer patients. Therefore, we applied this technology to study tissues from renal cell carcinomas (RCC) in comparison to healthy controls. We found that different biomarkers are identified from tissues than those previously identified in serum, and that serum markers are often not produced by the tumors themselves at detectable levels, reflecting the nonspecific nature of many circulating biomarkers. We detected and characterized αB-crystallin as an overexpressed protein in RCC tissues and showed differential expression by immunohistochemistry. We conclude that SELDI-TOF is more useful for the identification of biomarkers that are synthesized by diseased tissues than for the identification of serum biomarkers and identifies a separate set of markers. We suggest that SELDI-TOF should be used to screen human cancer tissues to identify potential tissue-specific proteins and simpler and more sensitive techniques can then be applied to determine their validity as biomarkers in biological fluids.

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Fahmy, Nader, Mark Woo, Mona Alameldin, King Chien Joe Lee, Kyle MacDonald, Lee W. Goneau, Peter Cadieux, Jeremy Burton et Stephen E. Pautler. « Endogenous biotin expression in renal and testicular tumors and literature review ». Canadian Urological Association Journal 8, n^o 7-8 (11 août 2014) : 268. http://dx.doi.org/10.5489/cuaj.1810.

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Introduction: The aim of this study was to examine endogenous biotin levels in tumour specimens collected from patients with renal and testicular tumours and compare them to the surrounding non-neoplastic surgical margin.Methods: Frozen samples were obtained from the Ontario Tumour Bank. Renal and testicular tumour tissue were included in this study. Normal tissue from the negative surgical margins of each tumour served as a control. Biotin detection in tissue specimens was determined using immunohistochemistry (IHC).Results: Specimens collected from 56 patients (36 men and 20 women) were included in this study. Histopathology of the 52 renal tumours included 31 (60%) conventional type RCC, 5 (10%) chromophobe RCC, 5 (10%) papillary RCC, 1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4 testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non-seminomatous germ cell tumours.Conclusion: No biotin signal was perceived in all tested tumour samples. Endogenous biotin expression was detected in the matching non-neoplastic surgical margin of tested renal tissues. This lack of staining may prove to be a valuable tool in future studies.

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Yang, Fafen, Yuke Chen, Linxue Luo, Shengbin Nong et Tong Li. « circFOXO3 Induced by KLF16 Modulates Clear Cell Renal Cell Carcinoma Growth and Natural Killer Cell Cytotoxic Activity through Sponging miR-29a-3p and miR-122-5p ». Disease Markers 2022 (29 août 2022) : 1–24. http://dx.doi.org/10.1155/2022/6062236.

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Renal cell carcinoma (RCC) is one of the most common urological malignancies with high incidence and metastatic relapse. Clear cell RCC (ccRCC) comprises nearly 70% of all RCC cases and is responsible for the majority of morbidity and mortality of RCC. Due to the poor diagnosis strategy and unsatisfactory clinical intervention, ccRCC causes a huge economic burden and poor patient quality of life; therefore, novel diagnostic or therapeutic targets for ccRCC are urgently needed. This study investigated the biological role of circFOXO3 in ccRCC development, showing that circFOXO3 is highly expressed in RCC cells and tissues and inhibits the viability of ccRCC cells. circFOXO3 dysregulation regulates NK cell cytotoxicity towards RCC cells by directly sponging miR-29a-3p and miR-122-5p. Overexpression of miR-29a-3p or miR-122-5p attenuated NK cell toxicity towards RCC cells and the transcriptional factor Kruppel-Like Factor 16 (KLF16) regulates circFOXO3 expression in RCC cells. In conclusion, this study has partially elucidated the function of circFOXO3 in ccRCC development, providing potential novel therapeutic targets for ccRCC.

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Piccinini, Lino, Gabriele Luppi, Alessandra Zoboli et Pietro Torricelli. « Occasional Diagnosis of Synchronous Renal Cell Carcinoma during Staging of Other Primary Tumors ». Tumori Journal 82, n^o 5 (septembre 1996) : 488–90. http://dx.doi.org/10.1177/030089169608200516.

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Synchronous renal cell cancer (RCC) associated with primary neoplasms of other organs or tissues represents a rare diagnostic report during life. Recently, the widespread use of new diagnostic techniques (echography, computed tomography and magnetic resonance imaging) has permitted diagnosis of clinically silent RCC. We report 6 RCC cases occasionally diagnosed during initial staging of a primary cancer of other organs: 1 rhinopharyngeal carcinoma, 1 gastric cancer, 1 Waldenstrom's disease, 1 non-Hodgkin's lymphoma, 2 breast cancer. RCC was clinically silent in all patients. The diagnostic problems related to a report of a renal mass in patients with neoplastic disease at other sites and the consequent therapeutic implications are discussed.

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Fang, Li, Ting Ye et Yanmei An. « Circular RNA FOXP1 Induced by ZNF263 Upregulates U2AF2 Expression to Accelerate Renal Cell Carcinoma Tumorigenesis and Warburg Effect through Sponging miR-423-5p ». Journal of Immunology Research 2021 (3 septembre 2021) : 1–16. http://dx.doi.org/10.1155/2021/8050993.

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Renal cell carcinoma (RCC), as one of the most common malignant tumors in the urinary system, is featured with high morbidity and mortality. Although the improvement of clinical intervention, such as surgery technology, chemotherapy, and radiotherapy, has been made, the outcomes of RCC patients are still poor. Novel targets for RCC treatment are urgently needed. Recently, circRNA has been in-depth studied and is considered as a promising direction for gene target therapy. In this study, we explored the function of circFOXP1 in RCC progression and its underlying mechanisms. Firstly, we demonstrated the characterization and expression of circFOXP1 in RCC tissues and cells. Next, by conducting a serial experiment, we found that downregulated circFOXP1 inhibited cell proliferation, migration, invasion, and the Warburg effect. Next, our experiments found that circFOXP1 upregulated U2AF2 expression via sponging miR-423-5p in RCC cells. Moreover, we found that ZNF263 induced circFOXP1 expression in RCC cells. To sum up, our study partially demonstrated that the novel ZNF263/circFOXP1/miR-423-5p/U2AF2 axis has a role in RCC progression. Our results might provide a new direction for RCC therapeutic target exploring.

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