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1
Zhang, Changyu, Qiang-Zhe Zhang, Kun Zhang, Lu-Yuan Li, Michael D. Pluth, Long Yi, and Zhen Xi. "Dual-biomarker-triggered fluorescence probes for differentiating cancer cells and revealing synergistic antioxidant effects under oxidative stress." Chemical Science 10, no. 7 (2019): 1945–52. http://dx.doi.org/10.1039/c8sc03781g.
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Rostron, Brian L., Jia Wang, Arash Etemadi, Sapna Thakur, Joanne T. Chang, Deepak Bhandari, Julianne Cook Botelho, et al. "Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study." International Journal of Environmental Research and Public Health 18, no. 14 (July 9, 2021): 7349. http://dx.doi.org/10.3390/ijerph18147349.
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Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case–control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds’ ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use.
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Karagkounis, Georgios, and Matthew Kalady. "Molecular Biology: Are We Getting Any Closer to Providing Clinically Useful Information?" Clinics in Colon and Rectal Surgery 30, no. 05 (November 2017): 415–22. http://dx.doi.org/10.1055/s-0037-1606373.
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AbstractAdvances in molecular biology and biomarker research have significantly impacted our understanding and treatment of multiple solid malignancies. In rectal cancer, where neoadjuvant chemoradiation is widely used for locally advanced disease, most efforts have focused on the identification of predictors of response in an attempt to appropriately select patients for multimodality therapy. A variety of biomarkers have been studied, including genetic mutations, chromosomal copy number alterations, and single as well as multigene expression patterns. Also, as transanal resection of rectal tumors requires accurate preoperative detection of lymph node metastasis, the identification of biomarkers of regional nodal involvement has been another important field of active research. While preliminary results have been promising, lack of external validation means has a limited translation to clinical use. This review summarizes recent developments in rectal cancer biomarker research, highlighting the challenges associated with their adoption, and evaluating their potential for clinical use.
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Yarden, Ronit, and Tamara Springer. "Precision medicine in colorectal cancer: Gaps in patients’ literacy of biomarkers and genetic testing." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 55. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.55.
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55 Background: Colorectal cancer (CRC) is the second leading cause of cancer death in the united states. Despite some advances, mortality is high and the 5-year overall survival from metastatic disease (mCRC) is only 14%. CRC is a heterogeneous disease with multiple subtypes defined by location, microsatellite integrity, specific genetic alterations and potentially age. The identification of specific driving mutation/s led to the development of targeted therapies. Patients are eligible for these treatments based on their personalized tumor biomarker profile. ASCO guidelines recommend that all patients with mCRC are tested for KRAS mutations. This mutation is present in ~40% of CRC patients, and serves as a biomarker for lack of response to EGFR therapy. Similarly, high microsatellite instability (MSI-H) suggests an inferior response to commonly used chemotherapy and favorable response to immunotherapy. Methods: We conducted an online survey to assess patients, survivors and caregivers’ knowledge and understanding of biomarker testing. Results: Among the 210 participants in this cross-sectional study, 81% of participants reported ‘no familiarity’ with the term biomarkers at the time of diagnosis, while 73% reported awareness at the time of the survey. Yet, when presented with specific biomarkers, majority of participants were not familiar with any of those biomarkers. Of the 103 stage IV respondents, only 14% were familiar with the four common CRC biomarkers, and only 1 in 4 reported their tumor was tested prior to treatment initiation. Nearly half of the respondents cited their physician and medical team as the main source of biomarker information (46%) while the other half reported their medical team never informed them of biomarkers. Overall, 50% of participants indicated that advocacy groups, medical websites, and various online resources were their main sources of biomarker information. Disparities of biomarker awareness were noted based on gender, age, and area of residency. Conclusions: Taken together, patients do not fully comprehend the meaning and implications of biomarker testing. Medical teams should make a greater effort to inform their patients early on in their treatment.
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Liang, Shujing, Lifang Hu, Zixiang Wu, Zhihao Chen, Shuyu Liu, Xia Xu, and Airong Qian. "CDK12: A Potent Target and Biomarker for Human Cancer Therapy." Cells 9, no. 6 (June 18, 2020): 1483. http://dx.doi.org/10.3390/cells9061483.
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Cyclin-dependent kinases (CDKs) are a group of serine/threonine protein kinases and play crucial roles in various cellular processes by regulating cell cycle and gene transcription. Cyclin-dependent kinase 12 (CDK12) is an important transcription-associated CDK. It shows versatile roles in regulating gene transcription, RNA splicing, translation, DNA damage response (DDR), cell cycle progression and cell proliferation. Recently, increasing evidence demonstrates the important role of CDK12 in various human cancers, illustrating it as both a biomarker of cancer and a potential target for cancer therapy. Here, we summarize the current knowledge of CDK12, and review the research advances of CDK12′s biological functions, especially its role in human cancers and as a potential target and biomarker for cancer therapy.
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Bickel, Hubert, Wolfgang Bogner, Peter Christian Dubsky, Rupert Bartsch, Margaretha Rudas, Thomas Helbich, and Katja Pinker-Domenig. "Diffusion-weighted imaging using ADC mapping as an imaging biomarker for breast cancer invasiveness." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 11093. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.11093.
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11093 Background: Recently, functional imaging techniques such as diffusion weighted imaging (DWI) have been added to routine MR and have shown great potential for improving breast cancer diagnosis. DWI depicts cellular diffusivity on a molecular level and can be quantified using the apparent diffusion coefficient (ADC). In malignant tumors diffusivity is restricted, leading to lower ADC values than benign tumors. The aim of this study was to proof, that DWI can be used to differentiate benign from malignant tumors and to elucidate if ADC can serve as an imaging biomarker for breast cancer invasiveness. Methods: In this IRB-approved study 250 patients with 267 suspicious breast lesions (BI-RADS IV-V) were included. All patients underwent routine MR at 3T. A DWI-sequence was added to a standard imaging protocol, increasing measurement time by 2:30 min. The lesions were identified in routine MR and DWI sequences and ADC values of the lesions were calculated. Histopathology was used as the standard of reference for all lesions. Appropriate statistical tests were used to compare the ADC values of benign and malignant tumors (cut-off value 1.25×10-3mm²/s), of invasive and non-invasive disease and between different invasive tumor subtypes. Results: There were 91 benign (mean ADC 1.58×10-3mm²/s) and 176 malignant (.94×10-3mm²/s) lesions, sensitivity and specificity were 94.3% (PPV 95.4%, CI 0.91-0.98) and 91.2% (NPV 89.2%, CI 0.81-0.94). 155 lesions were invasive cancers (median ADC .90×10-3mm²/s), while 21 were non-invasive ductal carcinoma in situ (1.22×10-3mm²/s). The invasive cancers were 130 invasive ductal (median ADC .91×10-3mm²/s) and 25 invasive lobular cancers (.83×10-3mm²/s). ADC was significantly different between benign and malignant lesions (p<.001) and between invasive and non-invasive cancers (p<.001), while no significant difference could be found between the invasive cancer subtypes (p=.163). Conclusions: Diffusion-weighted imaging reliably allows differentiation of benign and malignant breast tumors. The data suggest that ADC can be used as a non-invasive imaging biomarker for breast cancer invasiveness and may be of importance to treatment planning and outcome in breast cancer patients.
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Vallejo Morales, Esteban, Gustavo Suárez Guerrero, and Lina M. Hoyos Palacio. "Computational Simulation of Colorectal Cancer Biomarker Particle Mobility in a 3D Model." Molecules 28, no. 2 (January 6, 2023): 589. http://dx.doi.org/10.3390/molecules28020589.
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Even though some methods for the detection of colorectal cancer have been used clinically, most of the techniques used do not consider the in situ detection of colorectal cancer (CRC) biomarkers, which would favor in vivo real-time monitoring of the carcinogenesis process and consequent studies of the disease. In order to give a scientific and computational framework ideal for the evaluation of diagnosis techniques based on the early detection of biomarker molecules modeled as spherical particles from the computational point of view, a computational representation of the rectum, stool and biomarker particles was developed. As consequence of the transport of stool, there was a displacement of CRC biomarker particles that entered the system as a result of the cellular apoptosis processes in polyps with a length lower than 1 cm, reaching a maximum velocity of 3.47×10−3 m/s. The biomarkers studied showed trajectories distant to regions of the polyp of origin in 1 min of simulation. The research results show that the biomarker particles for CRC respond to the variations in the movements of the stool with trajectories and speeds that depend on the location of the injury, which will allow locating the regions with the highest possibilities of catching particles through in situ measurement instruments in the future.
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Boehm, Brock E., Monica E. York, Gyorgy Petrovics, Indu Kohaar, and Gregory T. Chesnut. "Biomarkers of Aggressive Prostate Cancer at Diagnosis." International Journal of Molecular Sciences 24, no. 3 (January 22, 2023): 2185. http://dx.doi.org/10.3390/ijms24032185.
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In the United States, prostate cancer (CaP) remains the second leading cause of cancer deaths in men. CaP is predominantly indolent at diagnosis, with a small fraction (25–30%) representing an aggressive subtype (Gleason score 7–10) that is prone to metastatic progression. This fact, coupled with the criticism surrounding the role of prostate-specific antigenin prostate cancer screening, demonstrates the current need for a biomarker(s) that can identify clinically significant CaP and avoid unnecessary biopsy procedures and psychological implications of being diagnosed with low-risk prostate cancer. Although several diagnostic biomarkers are available to clinicians, very few comparative trials have been performed to assess the clinical effectiveness of these biomarkers. It is of note, however, that a majority of these clinical trials have been over-represented by men of Caucasian origin, despite the fact that African American men have a 1.7 times higher incidence and 2.1 timeshigher rate of mortality from prostate cancer. Biomarkers for CaP diagnosis based on the tissue of origin include urine-based gene expression assays (PCA3, Select MDx, ExoDx Prostate IntelliScore, Mi-Prostate Score, PCA3-PCGEM1 gene panel), blood-based protein biomarkers (4K, PHI), and tissue-based DNA biomarker (Confirm MDx). Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.
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Aliyu, Mansur, Ali Akbar Saboor-Yaraghi, Shima Nejati, and Behrouz Robat-Jazi. "Urinary VPAC1: A potential biomarker in prostate cancer." AIMS Allergy and Immunology 6, no. 2 (2022): 42–63. http://dx.doi.org/10.3934/allergy.2022006.
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<abstract> <p>Prostate cancer is ranked as the fourth most prevalent cancer commonly diagnosed among males over 40 years of age, according to the WHO Cancer Fact Sheet 2020, and it is additionally a leading cause of cancer mortality among males. The incidence of prostate cancer and mortality varied significantly across the globe. Diagnosis of prostate cancer hinders easier management of cases, and prostate-specific antigen (PSA) use for screening of prostate cancer has poor specificity and sensitivity, thereby yielding overdiagnosis and unnecessary biopsies. Radiologically guided (ultrasound/MRI) prostate biopsy, considered the gold standard, is invasive and can miss a significant number of metastatic cancers. Even though mild, other prostate biopsy complications occur on a large scale, and few severe ones are often recorded. Scientists intensify their search for biomarker(s) for non-invasive diagnosis of prostate cancer using proteomics, metabolomics, genomics, and bioinformatics—urinary biomarkers were uniquely on the lookout. Vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptor 1 (VPAC1), which is overexpressed (a thousandfold) in prostate cancer at the onset of oncogenesis and is excreted in the urine on tumor cells, is a contender in the prostate cancer biomarker quest. VPAC1 is ubiquitous, expressed by normal and malignant cells, and interwoven in their cell membranes. Therefore, using urine samples limits the possibility of making the wrong diagnosis, since VPAC1 is not normally excreted in the urine. Nevertheless, studying transmembrane receptors is intricate. However, producing monoclonal antibodies against the N-terminal end of VPAC1 can provide a promising target for designing a non-invasive diagnostic assay for early detection of prostate cancer using a urine sample.</p> </abstract>
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Acharya, Devansh, Haoran Gao, Rick Dean Jorgensen, Muhammad Hamdan, Hussein Al-Ahmad, Brittani Thomas, Ushasree Chamarthy, Venugopal Gangur, and Gordan Srkalovic. "Analysis of immune biomarkers in cancer patients with solid tumors versus healthy subjects." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 68.19. http://dx.doi.org/10.4049/jimmunol.206.supp.68.19.
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Abstract Cytokines and other immune regulatory molecules are critical players in the immune response against cancer. There is growing interest in testing the potential utility of systemic immune biomarkers to track cancer progression and to use them as predictors of effective responses to cancer therapy. The central hypothesis guiding this project is that specific immune biomarkers will serve as predictors of effective vs. ineffective immunotherapy in patients with malignant diseases. The objective of this study was to establish baseline of immune markers in patients already started treatment with immunotherapy (n=10) (T), patients starting, but not yet treated (S) with immunotherapy (n=10) and subjects without diagnosed malignant disease (W) (n=10). Blood was collected and plasma was isolated and used in the biomarker (100 markers) analysis using a protein microarray method (RayBiotech). The biomarkers in the three groups were analyzed by Principal Component Analysis, heat map with clustering, and differential expression based on p value, and Significance Analysis of Microarrays (SAM). Although 15 biomarkers were significantly different between S vs. W groups, based on SAM, only seven were found differentially expressed. Similarly, although 10 biomarkers were significantly different between T vs. W groups, based on SAM, only one biomarker was found differentially expressed. Furthermore, SAM revealed that responders (n=4) vs. stable (n=5) subgroup of patients within the T group exhibited 22 differentially expressed biomarkers. Future larger studies will be needed to evaluate whether immune markers will be able to predict effective vs. ineffective responses to immunotherapy and whether they may have therapeutic potential.
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Kurlinkus, Benediktas, Marija Ger, Algirdas Kaupinis, Eugenijus Jasiunas, Mindaugas Valius, and Audrius Sileikis. "CEACAM6’s Role as a Chemoresistance and Prognostic Biomarker for Pancreatic Cancer: A Comparison of CEACAM6’s Diagnostic and Prognostic Capabilities with Those of CA19-9 and CEA." Life 11, no. 6 (June 9, 2021): 542. http://dx.doi.org/10.3390/life11060542.
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Survival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, 267 patients were included in the study. Surgically collected pancreatic tissue samples were analysed via high-definition mass spectrometry. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was discovered as a possible promising pancreatic cancer biomarker. The predominance of CEACAM6 to pancreatic cancer was validated using antibodies in tissue samples. CEACAM6, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) blood serum concentrations were evaluated for clinical evaluation and comparison. Kaplan–Meier survival analyses were used to evaluate disease-free survival (DFS) and overall survival (OS). Poorer overall survival was significantly dependent on increased CEACAM6 blood serum concentrations (17.0 vs. 12.6 months, p = 0.017) in pancreatic cancer patients after radical treatment and adjuvant chemotherapy. Increased CEA and CA19-9 concentrations showed no significant dependencies with survival. Thus, CEACAM6 is a promising new biomarker with significant prognostic value and prediction of chemoresistance properties, enabling the improvement of individualised approaches to patients with pancreatic cancer.
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Roy, Roopali, Jiang Yang, and Marsha A. Moses. "Matrix Metalloproteinases As Novel Biomarker s and Potential Therapeutic Targets in Human Cancer." Journal of Clinical Oncology 27, no. 31 (November 1, 2009): 5287–97. http://dx.doi.org/10.1200/jco.2009.23.5556.
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The matrix metalloproteinase (MMP) family of enzymes is comprised of critically important extracellular matrix remodeling proteases whose activity has been implicated in a number of key normal and pathologic processes. The latter include tumor growth, progression, and metastasis as well as the dysregulated angiogenesis that is associated with these events. As a result, these proteases have come to represent important therapeutic and diagnostic targets for the treatment and detection of human cancers. In this review, we summarize the literature that establishes these enzymes as important clinical targets, discuss the complexity surrounding their choice as such, and chronicle the development strategies and outcomes of their clinical testing to date. The status of the MMP inhibitors currently in US Food and Drug Administration approved clinical trials is presented and reviewed. We also discuss the more recent and successful targeting of this enzyme family as diagnostic and prognostic predictors of human cancer, its status, and its stage. This analysis includes a wide variety of human cancers and a number of human sample types including tissue, plasma, serum, and urine.
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Sayyid, Rashid K., Abdallah K. Sayyid, Zachary Klaassen, Karen Hersey, Hanan Goldberg, Nathan Perlis, Ardalanejaz Ahmad, et al. "Replacing surveillance cystoscopy with urinary biomarkers in followup of patients with non-muscle-invasive bladder cancer: Patients’ and urologic oncologists’ perspectives." Canadian Urological Association Journal 12, no. 5 (February 2, 2018): E210–8. http://dx.doi.org/10.5489/cuaj.4922.
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Introduction: Urinary biomarkers are being developed to detect bladder cancer recurrence/progression in patients with non-muscle- invasive bladder cancer (NMIBC). We conducted a questionnaire- based study to determine what diagnostic accuracy and cost would such test(s) need for both patients and urologic oncologists to comfortably forgo surveillance cystoscopy in favour of these tests.Methods: Surveys were administered to NMIBC patients at followup cystoscopy visit and to physician members of the Society of Urologic Oncology. Participants were questioned about acceptable false-negative (FN) rates and costs for such alternatives, in addition to demographics that could influence chosen error rates and costs.Results: A total of 137 patient and 51 urologic oncologist responses were obtained. Seventy-seven percent of patients were not comfortable with urinary biomarker(s) alternatives to repeat cystoscopy, with a further 14% willing to accept such alternatives only if the FN rate were 0.5% or lower. Seventy-five percent of urologic oncologists were comfortable with an alternative urinary biomarker test(s), with 37% and 33% willing to accept FN rates of 5% and 1%, respectively. Forty-seven percent of patients were not willing to pay out-of-pocket for such tests, while 61% of urologic oncologists felt that a price range of $100–500 would be reasonable.Conclusions: This is the first survey evaluating patient and urologic oncologist perspectives on acceptable error rates and costs for urinary biomarker alternatives to surveillance cystoscopy for patients with NMIBC. Despite potential responder bias, this study suggests that urinary biomarker(s) will require sensitivity equivalent to that of cystoscopy in order to completely replace it in surveillance of patients with NMIBC.
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Wong, D. T., L. Zhang, J. Farrell, H. Zhou, D. Elashoff, K. Gao, and B. Paster. "Salivary biomarkers for pancreatic cancer detection." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 4630. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.4630.
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4630 Pancreatic cancer is the 4th leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. We evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for pancreatic cancer detection. Biomarker discovery strategies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133+2.0 array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P < 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P < 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. More importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P < 0.0001) with 92.9% sensitivity and 85.5% specificity. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer. No significant financial relationships to disclose.
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Onofrei, Pavel, Elena Carmen Cotrutz, Ana Emanuela Botez, Vasile Bogdan Grecu, Carmen Solcan, Anca Ileana Sin, Daniela Cristina Dimitriu, et al. "Maspin and Ezrina - Biomarker Molecules in Colorectal Cancer Correlative immunohistochemical study." Revista de Chimie 70, no. 8 (September 15, 2019): 2926–33. http://dx.doi.org/10.37358/rc.19.8.7458.
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The results of the recent years researches support the need for personalized therapeutic of cancer by completing the clinical, imagistic and histopathological diagnosis with molecular studies to identify new useful biomarkers for diagnosis, prognosis and tumor progression. Maspin is a non-inhibitory serine protease having a proapoptotic activity, suppressor of tumor invasion, metastasis and angiogenesis. Ezrin is a member of Ezrin/Radixin/Moesin (ERM) family, involved in cellular adhesion mechanisms, motility and invasiveness of tumor cells. In colorectal tumors, there is a heterogeneity of research results regarding the clinical significance of the maspin due to a possible partnership with other molecules with which it interacts through the same signaling pathways. Our study investigated the two molecule�s immunoreactivity (IR) in 92 colorectal tumors highlighting an inverse correlation between ezrin�s and maspin�s expression, suggesting the fact that ezrin�s overexpression could influence maspin�s tumoral suppressor role. Furthermore there was observed a difference of the molecules IR within the same tumoral stage, suggesting their utility regarding the treatment protocol of these tumors.
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Addo, Michael Kofi Darko, Ivy Antwi, and Gregory Bishop. "An Electrochemical Immunoassay System for Measuring Circulating Protein Biomarkers of Pediatric Soft Tissue Sarcoma." ECS Meeting Abstracts MA2022-02, no. 64 (October 9, 2022): 2394. http://dx.doi.org/10.1149/ma2022-02642394mtgabs.
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The combination of simple, inexpensive 3D-printed flow cells with electrochemical biosensors has recently emerged a promising strategy for detecting molecular biomarkers of disease. In this study, we report a multiplex electrochemical immunoassay based on pencil graphite electrode arrays, 3D-printed flow cells and magnetic bead bioconjugates for simultaneous detection of three biomarker proteins (cancer antigen 125 (CA-125), midkine (MK) and osteopontin (OPN)) linked to pediatric soft tissue sarcoma (PSTS). Magnetic bead bioconjugates are functionalized with large amounts of antibody and enzyme labels according to a previously reported strategy,1 pencil graphite electrodes are modified with gold nanoparticles and antibodies for specific capture of bioconjugate-labeled biomarkers, and 3D-printed flow cells to facilitate amperometric detection. Using this immunoassay platform, detection limits for CA-125, MK and OPN that are 100 times lower than those obtained using commercial enzyme-linked immunosorbent assay (ELISA) can be achieved. The combination of low-cost pencil graphite electrode arrays with the convenience of multi-labeled magnetic bead bioconjugates and simplicity of 3D-printed flow-cells results in a promising electrochemical biosensing strategy for biomarker proteins CA-125, MK, and OPN in human serum samples. Reference (1) Malhotra, R.; Patel, V.; Chikkaveeraiah, B. v.; Munge, B. S.; Cheong, S. C.; Zain, R. B.; Abraham, M. T.; Dey, D. K.; Gutkind, J. S.; Rusling, J. F. Ultrasensitive Detection of Cancer Biomarkers in the Clinic by Use of a Nanostructured Microfluidic Array. Analytical Chemistry 2012, 84 (14), 6249–6255. https://doi.org/10.1021/ac301392g.
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Lin, Jiunn-Chang, Pei-Ming Yang, and Tsang-Pai Liu. "PERK/ATF4-Dependent ZFAS1 Upregulation Is Associated with Sorafenib Resistance in Hepatocellular Carcinoma Cells." International Journal of Molecular Sciences 22, no. 11 (May 29, 2021): 5848. http://dx.doi.org/10.3390/ijms22115848.
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Sorafenib, a multi-kinase inhibitor, is the first-line treatment for advanced hepatocellular carcinoma (HCC) patients. However, this drug only provides a short improvement of patients’ overall survival, and drug resistance is commonly developed. Thus, the identification of resistant factor(s) or biomarker(s) is needed to develop more efficient therapeutic strategies. Long, non-coding RNAs (lncRNAs) have recently been viewed as attractive cancer biomarkers and drive many important cancer phenotypes. A lncRNA, ZFAS1 (ZNFX1 antisense RNA 1) has been found to promote HCC metastasis. This study found that sorafenib induced ZFAS1 expression specifically in sorafenib-resistant HCC cells. Although ZFAS1 knockdown did not restore the sensitivity of HCC cells to sorafenib, its expression may act as a resistant biomarker for sorafenib therapy. Bioinformatics analysis predicted that sorafenib tended to induce pathways related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in sorafenib-resistant HCC cells. In vitro experimental evidence suggested that sorafenib induced protein kinase RNA-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-dependent ZFAS1 expression, and sorafenib resistance could be overcome by PERK/ATF inhibitors. Therefore, PERK/ATF4/ZFAS1 signaling axis might be an attractive therapeutic and prognostic biomarker for sorafenib therapy in HCC.
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Essa, Hafsa Yousif Solayman, Gunay Kusaf, Ozel Yuruker, and Rasime Kalkan. "Epigenetic Alteration in Colorectal Cancer: A Biomarker for Diagnostic and Therapeutic Application." Global Medical Genetics 09, no. 03 (September 2022): 258–62. http://dx.doi.org/10.1055/s-0042-1757404.
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AbstractColorectal cancer (CRC) is the leading cause of cancer death worldwide. A crucial process that initiates and progresses CRC is various epigenetic and genetic changes occurring in colon epithelial cells. Recently, huge progress has been made to understand cancer epigenetics, especially regarding DNA methylation changes, histone modifications, dysregulation of miRNAs and noncoding RNAs. In the “epigenome” of colon cancer, abnormal methylation of genes that cause gene alterations or expression of miRNA has been reported in nearly all CRC; these findings can be encountered in the average CRC methylome. Epigenetic changes, known as driving events, are assumed to play a dominant part in CRC. Furthermore, as epigenetic changes in CRC become properly understood, these changes are being established as clinical biomarkers for therapeutic and diagnostic purposes. Progression in this area indicates that epigenetic changes will often be utilized in the future to prevent and treat CRC.
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Grinspan, Lauren Tal, and Augusto Villanueva. "Biomarker Development Using Liquid Biopsy in Hepatocellular Carcinoma." Seminars in Liver Disease 42, no. 02 (May 2022): 188–201. http://dx.doi.org/10.1055/s-0042-1748924.
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Liver cancer incidence rate continues to increase and currently ranks third in the total number of annual deaths, behind only lung and colorectal cancer. Most patients with hepatocellular carcinoma (HCC) are diagnosed at advanced stages, and they live for less than 2 years after diagnosis on average. This contrasts with those diagnosed at an early stage, who can be cured with surgery. However, even after curative resection, there remains a risk of up to 70% of postoperative HCC recurrence. There have been major changes in the management of HCC in the past 5 years, particularly for patients at advanced stages. Despite this multitude of new therapies, there is a lack of clear biomarkers to guide providers on the best approach to sequence therapies, which would maximize efficacy while minimizing toxicity. There are several areas in clinical management of HCC that are particularly challenging, and would benefit from development and implementation of new biomarkers to improve patient overall survival. Here, we review the major advances in liquid biopsy biomarkers for early detection of HCC, minimum residual disease, and predicting response to treatment.
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Verma, Shiv Shankar, Eswar Shankar, Spencer Lin, Vaibhav Singh, E. Ricky Chan, Shufen Cao, Gregory T. MacLennan, Lee E. Ponsky, and Sanjay Gupta. "Abstract 5168: Assessment and prognostic implication of 3-gene signature identified as potential biomarker in bladder cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5168. http://dx.doi.org/10.1158/1538-7445.am2022-5168.
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Abstract The majority of bladder cancers present with non-muscle invasive disease (NIMBC) confined to the superficial layers of the bladder wall, however, 50-70% of patients will subsequently progress to muscle-invasive bladder cancer (MIBC) that will require more aggressive treatment. For patient stratification, the current prognostication relies on tumor stage and grade, which remains challenging due to the lack of appropriate biomarker(s) to monitor disease progress. Therefore, there is an urgent need for predictive biomarkers that can distinguish between progressive versus non-progressive disease for the identification of patients to better stratify their risk of progression. Here we aim to identify novel prognostic biomarker(s) associated with disease progression by exploring bladder cancer patient gene expression database. We explored and analyzed the transcriptomic gene expression of bladder cancer patient datasets consisting of NIMBC and MIBC subtype from the NCBI GEO (GSE154261, GSE57813, and GSE37317) database. These datasets were analyzed using GEO2R (an R-based web application) and Limma R packages. Pathway enrichment analysis of differentially expressed genes (DEGs) between the NMIBC and MIBC group was analyzed using the ingenuity pathway analysis (IPA), metascape web-based portal, and Cytoscape. The above finding was functionally validated in human bladder cancer cell lines; RT4 (transitional cell papilloma), J82 (transitional cell carcinoma), HT1197 (bladder carcinoma), and 253JB-V (metastatic phenotype) and compared with the relative expression ofUROtsa (benign) urothelial cell line. A total of 1516 DEGs were identified between non-muscle-invasive and muscle-invasive bladder cancer specimens. To identify genes of prognostic value, we performed Gene Ontology (GO) and Kyoto Gene and Genomic encyclopedia (KEGG)analysis. A total of seven genes including CDKN2A, CDC20, CTSV, FOXM1, MAGEA6, KRT23, and S100A9 were confirmed with strong prognostic values in bladder cancer and validated by qRT-PCR conducted in various human bladder cancer cells representing stage-specific disease progression. ULCAN, human protein atlas, and The Cancer Genome Atlas datasets were used to confirm the predictive value of these genes in bladder cancer progression. Moreover, Kaplan-Meier analysis and Cox-hazard ratio analysis were performed to determine the prognostic role of these genes. Univariate analysis performed on a validation set identified a 3-panel gene set viz. CDKN2A, CTSV and FOXM1 with 95.5% sensitivity and 100% specificity in predicting bladder cancer progression. Our study screened and confirmed a panel of a 3-genes biomarkers that could precisely predict the progression and prognosis of bladder cancer. Citation Format: Shiv Shankar Verma, Eswar Shankar, Spencer Lin, Vaibhav Singh, E. Ricky Chan, Shufen Cao, Gregory T MacLennan, Lee E. Ponsky, Sanjay Gupta. Assessment and prognostic implication of 3-gene signature identified as potential biomarker in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5168.
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Chan, J. K., D. S. Kapp, E. Mechetner, and I. Yu. "Biomarker and in vitro chemoresistance profiles of undifferentiated ovarian cancers." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 2532. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.2532.
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2532 Background: To determine the biomarker expression and drug resistance patterns of undifferentiated ovarian cancers. Methods: Biomarker expression was determined by immunohistochemistry. In vitro drug resistance profiles were analyzed by assays exposing tumors to suprapharmacologic doses of chemotherapy. Results: Of 177 ovarian cancer specimens, 63 were classified as undifferentiated tumors and 114 well-differentiated cancers were used for comparison. Of the undifferentiated tumors, 46.7% were primary cancers and the remainder were recurrent cancers. Most of the well-differentiated tumors were obtained from primary (82%) vs. recurrent disease specimens. The average DNA index and S-phase fraction were significantly higher in the undifferentiated vs. well-differentiated tumors (1.42 vs. 1.23, p=0.025 for DNA index; 1.69 vs. 3.06, p<0.0001 for S phase fraction). In addition, the percent of tumors with p53 mutations was also higher in the undifferentiated compared to the well-differentiated tumors (47.8% vs. 17.8%; p=0.005). The mean percent cell inhibition was significantly lower in the undifferentiated tumors compared to well-differentiated cancers after exposure to etoposide (54%±21 vs. 80%±18; p=0.0002), doxorubicin (59%±28 vs. 80.0%±21; p=0.07), and topotecan (61.7%±20 vs. 71%±21; p=0.015). Compared to well-differentiated tumors, undifferentiated tumors tended to be more resistant to etoposide (40% vs. 11%), doxorubicin (22% vs. 9%), and topotecan (19% vs. 16%). However, the drug resistance patterns after exposure to taxanes (paclitaxel and taxotere) and platinums (carboplatin and cisplatin) were similar. Conclusions: Undifferentiated tumors of the ovary have a significantly different biomarker expression and drug resistance profiles compared to well-differentiated tumors. Given that undifferentiated cancers provide a treatment challenge for the clinician, this data can provide additional prognostic and therapeutic information, and warrants further investigation. No significant financial relationships to disclose.
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Wilkinson, Richard D. A., Roberta E. Burden, Sara H. McDowell, Darragh G. McArt, Stephen McQuaid, Victoria Bingham, Rich Williams, et al. "A Novel Role for Cathepsin S as a Potential Biomarker in Triple Negative Breast Cancer." Journal of Oncology 2019 (June 27, 2019): 1–12. http://dx.doi.org/10.1155/2019/3980273.
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Cathepsin S (CTSS) has previously been implicated in a number of cancer types, where it is associated with poor clinical features and outcome. To date, patient outcome in breast cancer has not been examined with respect to this protease. Here, we carried out immunohistochemical (IHC) staining of CTSS using a breast cancer tissue microarray in patients who received adjuvant therapy. We scored CTSS expression in the epithelial and stromal compartments and evaluated the association of CTSS expression with matched clinical outcome data. We observed differences in outcome based on CTSS expression, with stromal-derived CTSS expression correlating with a poor outcome and epithelial CTSS expression associated with an improved outcome. Further subtype characterisation revealed high epithelial CTSS expression in TNBC patients with improved outcome, which remained consistent across two independent TMA cohorts. Furtherin silicogene expression analysis, using both in-house and publicly available datasets, confirmed these observations and suggested high CTSS expression may also be beneficial to outcome in ER-/HER2+ cancer. Furthermore, high CTSS expression was associated with the BL1 Lehmann subgroup, which is characterised by defects in DNA damage repair pathways and correlates with improved outcome. Finally, analysis of matching IHC analysis reveals an increased M1 (tumour destructive) polarisation in macrophage in patients exhibiting high epithelial CTSS expression. In conclusion, our observations suggest epithelial CTSS expression may be prognostic of improved outcome in TNBC. Improved outcome observed with HER2+ at the gene expression level furthermore suggests CTSS may be prognostic of improved outcome in ER- cancers as a whole. Lastly, from the context of these patients receiving adjuvant therapy and as a result of its association with BL1 subgroup CTSS may be elevated in patients with defects in DNA damage repair pathways, indicating it may be predictive of tumour sensitivity to DNA damaging agents.
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Cedano-Prieto, Dora Maria, Fernando Bergez-Hernandez, Emir Adolfo Leal-Leon, Noemi Garcia-Magallanes, Fred Luque-Ortega, Veronica Picos-Cardenas, Edna Guerrero-Arambula, Bricia Gutierrez-Zepeda, Enrique Romo-Martinez, and Eliakym Arambula-Meraz. "Altered Expression of Survivin Variants S-2B and S-WT in Breast Cancer Is Related to Adipokine Expression." Journal of Oncology 2022 (March 16, 2022): 1–10. http://dx.doi.org/10.1155/2022/7398444.
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Breast cancer (BCa) is one of the leading causes of death in women with these types of malignancies. Early detection is pivotal to improve prognosis and reduce mortality. Several proteins and genes have been proposed as biomarkers for cancer; however, further studies are required before a molecule is accepted as a definitive biomarker. This study was aimed at investigating the expression of survivin variants S-WT, S-2B, and S-ΔEx3, as well as adipokines LEP and ADIPOQ in breast cancer. Breast samples were obtained from patients with ( n = 27 ) and without ( n = 20 ) BCa, and relative gene expression was assessed by RT-qPCR. S-WT and S-2B showed a significant increase in BCa samples ( p = 0.005 and p = 0.001 , respectively) and in high-aggressiveness BCa ( p = 0.026 and p = 0.037 , respectively). Despite S-ΔEx3 expression remained globally unchanged, when dividing BCa samples according to the stage, this gene showed a significant tendency to increase towards more advanced stages, and the exact opposite effect was observed for LEP. Furthermore, LEP expression showed a negative correlation with S-2B ( p = 0.005 ) and S-WT ( p = 0.011 ), and in the same manner, ADIPOQ was negatively related with these two survivin variants ( p = 0.001 and p = 0.005 , respectively). Interestingly, S-ΔEx3 expression appears unaffected by LEP and ADIPOQ expressions. Our results highlight the importance of investigating specific variants of a given gene, as sequence variation may grant different correlation with other important structures and diseases.
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Bock, B., D. Hasdemir, F. Wandrer, T. Rodt, MP Manns, K. Schulze-Osthoff, and H. Bantel. "Serum Cell Death Biomarker Mirrors Liver Cancer Regression after Transarterial Chemoembolisation." Zeitschrift für Gastroenterologie 54, no. 12 (December 19, 2016): 1343–404. http://dx.doi.org/10.1055/s-0036-1597493.
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Greenberg, Alissa K., Binaya Rimal, Kevin Felner, Subooha Zafar, Jerry Hung, Ellen Eylers, Brendan Phalan, et al. "S-Adenosylmethionine as a Biomarker for the Early Detection of Lung Cancer." Chest 132, no. 4 (October 2007): 1247–52. http://dx.doi.org/10.1378/chest.07-0622.
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Carmicheal, Joseph, Asish Patel, Vipin Dalal, Pranita Atri, Amaninder S. Dhaliwal, Uwe A. Wittel, Mokenge P. Malafa, et al. "Elevating pancreatic cystic lesion stratification: Current and future pancreatic cancer biomarker(s)." Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1873, no. 1 (January 2020): 188318. http://dx.doi.org/10.1016/j.bbcan.2019.188318.
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Ramberg, Håkon, Elin Richardsen, Gustavo A. de Souza, Mehrdad Rakaee, Maria Ekman Stensland, Peder Rustøen Braadland, Ståle Nygård, et al. "Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer." Carcinogenesis 42, no. 5 (February 20, 2021): 685–93. http://dx.doi.org/10.1093/carcin/bgab015.
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Abstract The demographic shift toward an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years postsurgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein (MVP) was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the MVP was verified by scoring immunohistochemical staining of a tissue microarray. High level of MVP was associated with more than 4-fold higher risk for death from prostate cancer (hazard ratio = 4.41, 95% confidence interval: 1.45–13.38; P = 0.009) in a Cox proportional hazard models, adjusted for Cancer of the Prostate Risk Assessments Post-surgical (CAPRA-S) score and perineural invasion. Decision curve analyses suggested an improved standardized net benefit, ranging from 0.06 to 0.18, of adding MVP onto CAPRA-S score. This observation was confirmed by receiver operator characteristics curve analyses for the CAPRA-S score versus CAPRA-S and MVP score (area under the curve: 0.58 versus 0.73). From these analyses, one can infer that MVP levels in combination with CAPRA-S score might add onto established risk parameters to identify patients with lethal prostate cancer.
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Nitusca, Diana, Anca Marcu, Alis Dema, Loredana Balacescu, Ovidiu Balacescu, Razvan Bardan, Alin Adrian Cumpanas, et al. "Long Noncoding RNA NEAT1 as a Potential Candidate Biomarker for Prostate Cancer." Life 11, no. 4 (April 6, 2021): 320. http://dx.doi.org/10.3390/life11040320.
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Background: Prostate cancer (PCa) remains one of the leading causes of cancer-related mortality in men worldwide, mainly due to unsatisfactory diagnostic methods used at present, which lead to overdiagnosis, unnecessary biopsies and treatment, or misdiagnosis in early asymptomatic stages. New diagnostic biomarkers are needed for a correct and early diagnosis. Long noncoding RNAs (lncRNAs) have been broadly studied for their involvement in PCa biology, as well as for their potential role as diagnostic biomarkers. Methods: We conducted lncRNA profiling in plasma and microdissected formalin-fixed paraffin-embedded (FFPE) tissues of PCa patients and attempted validation for commonly dysregulated individual lncRNAs. Results: Plasma profiling revealed eight dysregulated lncRNAs, while microarray analysis revealed 717 significantly dysregulated lncRNAs, out of which only nuclear-enriched abundant transcript 1 (NEAT1) was commonly upregulated in plasma samples and FFPE tissues. NEAT1’s individual validation revealed statistically significant upregulation (FC = 2.101, p = 0.009). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) value of 0.7298 for NEAT1 (95% CI = 0.5812–0.8785), suggesting a relatively high diagnostic value, thus having a potential biomarker role for this malignancy. Conclusions: We present herein data suggesting that NEAT1 could serve as a diagnostic biomarker for PCa. Additional studies of larger cohorts are needed to confirm our findings, as well as the oncogenic mechanism of NEAT1 in the development of PCa.
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TAKEYAMA, HIROSHI, and YOSHINOBU MANOME. "Serum Sialyl Fibronectin Is an Indicator of Good Prognosis in Thyroid Cancer." Cancer Diagnosis & Prognosis 3, no. 1 (December 30, 2022): 75–84. http://dx.doi.org/10.21873/cdp.10182.
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Background/Aim: Sialyl-fibronectin (S-FN), a type of glycoprotein like Sialyl Lewisa and MAC1 thyroid cancer biomarkers, has been found to be expressed in thyroid cancer. In this study, we examined the usefulness of serum S-FN as a biomarker, as well as prognostic factor in various tumors including thyroid cancer. Patients and Methods: Using the MoAb JT-95, an ELISA kit was created and S-FN levels in sera (blood S-FN) of a total of 182 cases were investigated. Analysis included 63 cases of thyroid cancer, 33 cases of thyroid benign tumors, 7 cases of parathyroid benign tumors, and 79 cases of breast cancer. Results: The incidence of blood S-FN-positive cases was 24 (38.0%) in 63 examined patients with thyroid cancer. Out of 40 examined benign neck tumor cases, 16/40 (40%) were S-FN-positive. Out of 79 examined breast cancer cases, 20/79 (25.3%) were S-FN-positive, with significant differences between thyroid and breast cancer cases (p=0.007). Regarding the association of blood S-FN expression and prognosis in thyroid cancer, there was a significant difference between 39 blood S-FN-negative cases and 15 recurrent or metastatic cases in terms of progression and pathological factors: tumor size, lymph node metastasis, extra-membrane infiltration, and clinical stage. All 63 assessed thyroid cancer cases also had a significant difference in these factors. There were no significant differences between these factors in the 24 blood S-FN-positive thyroid cancer cases. In cases of recurrent metastasis, intravascular cells were observed in all recurrent metastasis patients of both groups. Regarding staining of intravascular infiltrating cells, recurrent metastasis appeared at a higher rate in cases with S-FN-negative infiltrating cells. Conclusion: S-FN presence in blood can be used as an indicator of good prognosis in thyroid cancer patients.
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Krabbe, Laura-Maria, Georgios Gakis, and Yair Lotan. "Clinical Utility of Bladder Cancer Biomarkers." Société Internationale d’Urologie Journal 1, no. 1 (October 13, 2020): 62–67. http://dx.doi.org/10.48083/vuvb4988.
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Each year, there are an estimated 550 000 diagnoses of bladder cancer worldwide, and almost 200 000 deaths from bladder cancer. The need for frequent follow-up, including invasive procedures like cystoscopy, repetitive procedures like transurethral resection of bladder tumors and intravesical instillation therapy in non-muscle invasive stages, as well as systemic treatment with or without radical local treatment in advanced stages, makes bladder cancer one of the most expensive cancers to treat. Prognostic and predictive biomarkers have the potential to fundamentally change bladder cancer treatment algorithms, which may result in improved patient comfort and oncological outcomes and may also decrease the socioeconomic burden of the disease. Intense research has resulted in the recent approval by the U. S. Food and Drug Administration of the first agent for this disease that targets a specific mutation (fibroblast-growth factor receptor). Yet, many areas of bladder cancer diagnosis and treatment have remained unchanged for decades, and this is only in part due to their therapeutic success. In order to integrate biomarkers into clinical practice patterns, specific considerations for the different disease stages and settings should be kept in mind. Especially in the setting of screening, work-up of hematuria, as well as surveillance of patients with non-muscle invasive bladder cancer, (urine-)biomarkers may prove useful. They must, however, demonstrate a high enough sensitivity to pick up a cancer diagnosis or recurrence, allow easy handling (preferably a point-of-care setting) and adequate cost–benefit relationships, while also providing additional information to a full work-up. A biomarker to identify patients with muscle invasive bladder cancer who are in need of—and likely to respond to—neoadjuvant therapy would be very useful. In later disease, early detection of recurrence or progression, as well as biomarkers guiding treatment decisions between the available systemic agents, will be paramount for improved patient care.
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Scieglinska, Dorota, Damian Robert Sojka, Agnieszka Gogler-Pigłowska, Vira Chumak, and Zdzisław Krawczyk. "Various Anti-HSPA2 Antibodies Yield Different Results in Studies on Cancer-Related Functions of Heat Shock Protein A2." International Journal of Molecular Sciences 21, no. 12 (June 16, 2020): 4296. http://dx.doi.org/10.3390/ijms21124296.
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Heat shock proteins (HSPs) constitute a major part of the molecular chaperone system and play a fundamental role in cell proteostasis. The HSPA (HSP70) family groups twelve highly homologous HSPA proteins. Certain HSPAs are regarded as important cancer-related proteins, prospective therapeutic targets for cancer treatment, and also as potential cancer biomarkers. Heat Shock Protein A2 (HSPA2), a testis-enriched chaperone and one of the least characterized members of the HSPA family, has recently emerged as an important cancer-relevant protein with potential biomarker significance. Nevertheless, conflicting conclusions have been recently drawn both according to HSPA2 role in cancer cells, as well as to its prognostic value. In this work we have shown that one of the serious limitations in HSPA2 protein research is cross-reactivity of antibodies marketed as specific for HSPA2 with one or more other HSPA(s). Among non-specific antibodies were also those recently used for HSPA2 detection in functional and biomarker studies. We showed how using non-specific antibodies can generate misleading conclusions on HSPA2 expression in non-stressed cancer cells and tumors, as well as in cancer cells exposed to proteotoxic stress. Our findings addressed concerns on some published studies dealing with HSPA2 as a cancer-related protein.
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Mahtani, Reshma L., Alexander Niyazov, Katie Lewis, Lucy Massey, Alex Rider, Bhakti Arondekar, and Michael P. Lux. "Impact of race on biomarker testing among HER2- advanced breast cancer (ABC) patients (pts) in the United States: Results from a real-world study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10598. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10598.
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10598 Background: African Americans (AA) have the highest breast cancer (BC) mortality rate. Access to treatment is a known contributing factor. In the past 4 years, several targeted therapies for HER2- BC have become available which require testing for specific biomarkers. This study assessed the impact of race on biomarker testing rates in HER2- ABC pts receiving treatment in the US. Methods: Oncologists were recruited to abstract data from medical charts for the next 8-10 pts receiving treatment with HER2- ABC during Sept 2019-Apr 2020. Pts records were stratified by race and categorized into 3 mutually exclusive cohorts [White/Caucasian (White), AA, Other]. The other race cohort was excluded from this analysis due to small sample size. Differences in pt demographics/clinical characteristics were analyzed via Fisher’s exact tests. Testing rates for actionable biomarkers (i.e. BRCA1/2, PIK3CA, PD-L1) were compared between White and AA pts utilizing logistic regressions controlling for age, known family history of a BRCA-related cancer, hormone receptor (HR) status and practice setting (academic vs. community). Further analyses by age will be presented. Results: This analysis included 378 pts records, provided by 40 oncologists. Mean age was 64 years; 77% had HR+/HER2- ABC; 20% had advanced triple negative breast cancer (TNBC), 3% had ABC with an unknown HR status. Compared to White pts, AA pts were significantly more likely to have advanced TNBC (27% vs. 18%, p<0.05). Compared to White pts, AA pts had significantly lower BRCA1/2 mutation (mut) testing rates (Table). Numerically lower rates of PIK3CAmut and PD-L1 testing were observed among AA pts (Table). BRCA1/2mut positivity rate (germline [g] and/or somatic [s]) was higher among AA vs. White pts (30% vs. 22%). Positivity rate for PIK3CAmut was lower for AA vs. White pts (8% vs. 11%). Conclusions: A higher than expected BRCA1/2mut positivity rate was observed than previously reported in the literature. This is likely because this analysis included s BRCA1/2mut and represented a high risk pt population. Across all biomarkers assessed, AA pts had lower testing rates than White pts. This suggests racial disparities in testing rates of actionable biomarkers. Consistent with guidelines, and with the increased availability of targeted therapies, focused efforts should be developed to increase biomarker testing in AA pts. Funding: Pfizer Biomarker Testing Rates by Race.[Table: see text]
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Al-Shehri, Fawziah S., and Eman M. Abd EL Azeem. "Activated Leukocyte Cell Adhesion Molecule (ALCAM) in Saudi Breast Cancer Patients as Prognostic and Predictive Indicator." Breast Cancer: Basic and Clinical Research 9 (January 2015): BCBCR.S25563. http://dx.doi.org/10.4137/bcbcr.s25563.
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Background Activated leukocyte cell adhesion molecules (ALCAMs) play an essential role in tumor metastasis and are higher in some patients with breast cancer. AIM This study aimed to evaluate ALCAM as an early diagnostic biomarker for breast cancer and how it compares with other markers. Subjects and Methods One-hundred and sixty-one women were selected for this study. They were divided into three groups: Group 1 consisted of 42 healthy individuals (control) while a patients groups divided into two groups according to tumour grade, Group II, Include 58 breast cancer patient's grade II and Group III, Include 61 patients with grade III of breast cancer. Tumour markers CEA, CA 15–3 and s ALCAM levels were determined and Group 2 consisted of breast cancer patients. Results A highly significant elevation was recorded in s ALCAM, CA 15–3 and CEA. Percent change for grade II and grade III were [sALCAM (90, 127)], [CA15–3 (40, 72)] and [CEA (33, 156)]. Operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the biomarkers ALCAM, CA15–3 and CEA with area under the curve (AUC) of (0.99 & 1.0) (AUC 0.947 & 0.99) and (AUC 0.88 & 0.94) for grade II and grade III respectively the incremental values of AUC were statistically highly significant (p < 0.001). Conclusion It could be concluded that serum ALCAM concentration represents a suitable biomarker for Saudi arabian breast carcinoma with high sensitivity and has the potential to be used as a diagnostic tool comparable to CA15–3 and CEA.
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Whited, Allison M., Kanwar Vikas Singh, David Evans, and Raj Solanki. "An Electronic Sensor for Detection of Early-Stage Biomarker/s for Ovarian Cancer." BioNanoScience 2, no. 4 (September 29, 2012): 161–70. http://dx.doi.org/10.1007/s12668-012-0049-2.
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Lee, Dae Ho. "Practical issues of biomarker-assisted targeted therapy in precision medicine and immuno-oncology era." ESMO Open 3, Suppl 1 (June 2018): e000370. http://dx.doi.org/10.1136/esmoopen-2018-000370.
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The concept of precision medicine is not new, as multiplex and very sensitive methods, or next-generation sequencing and matched targeted cancer therapies, have come to clinical practice. Substantial progress has been made from the discovery to the development and clinical application of biomarkers and matched targeted therapies. However, there still remain many challenges and issues to be overcome in each step, from acquisition of tumour tissues through validation of biomarkers to the final decision on targeted therapy. This review will briefly touch on these issues, hoping to provide a better understanding and application of targeted therapy in cancer treatment in the era of precision medicine and immuno-oncology.It also helps to understand that the meaning or value of biomarker(s) and matched targeted therapy changes along with expansion of knowledge and advance of methodology, and constant efforts have to be made in evaluating the meaning and clinical value during the development and after the establishment of biomarkers or the approval of matched targeted therapies, which might be more complicated by the advent of new therapeutic agents and new diagnostic methods.
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Lacroix, Romaric, Loris Vallier, Amandine Bonifay, Stephanie Simoncini, Diane Mege, Mathilde Aubert, Laurence Panicot-Dubois, Christophe Dubois, and Françoise Dignat-George. "Microvesicles and Cancer Associated Thrombosis." Seminars in Thrombosis and Hemostasis 45, no. 06 (August 20, 2019): 593–603. http://dx.doi.org/10.1055/s-0039-1693476.
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AbstractMicrovesicles (MVs) are small membrane enclosed structures released into the extracellular space by virtually all cell types. Their composition varies according to the cell origin and the stimulus which caused their formation. They harbor functional molecules and participate in intercellular communication. Endothelium, inflammatory cells, and cancer cells produce procoagulant MVs which contribute to cancer-associated thrombosis (CAT) in animal models. The tissue factor (TF) conveyed by these MVs was shown to play a key role in different animal models of experimental CAT. Alternatively, other molecular mechanisms involving polyphosphates or phosphatidylethanolamine could also be involved. In clinical practice, an association between an increase in the number of TF-positive or the procoagulant activity of these MVs and the occurrence of CAT has indeed been demonstrated in pancreatic-biliary cancers, suggesting that they could behave as a biomarker predictive for CAT. However, to date, this association was not confirmed in other types of cancer. Potential causes explaining this limited associated between MVs and CAT are (1) the diversity of mechanisms associating MVs and different types of cancer; (2) a more complex role of MVs in hemostasis integrating their anticoagulant and fibrinolytic activity; and (3) the lack of sensitivity, reproducibility, and standardization of current methodologies permitting measurement of MVs. Each of these hypotheses constitutes an interesting exploration path for a future reassessment of the clinical interest of the MVs in CAT.
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Liu, Hongyan, Simin Ai, Yajuan Liu, Hongmei Zeng, Huimei Da, Yaling Liu, Yaqin Chai, and Ruo Yuan. "Enhancing photoelectrochemical performance of ZnIn2S4 by phosphorus doping for sensitive detection of miRNA-155." Chemical Communications 56, no. 91 (2020): 14275–78. http://dx.doi.org/10.1039/d0cc06111e.
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Iwamoto, Hiroaki, Kouji Izumi, Ryunosuke Nakagawa, Ren Toriumi, Shuhei Aoyama, Taiki Kamijima, Takafumi Shimada, et al. "Serum CCL2 Is a Prognostic Biomarker for Non-Metastatic Castration-Sensitive Prostate Cancer." Biomedicines 10, no. 10 (September 22, 2022): 2369. http://dx.doi.org/10.3390/biomedicines10102369.
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Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it remains unclear whether it can be applied to non-metastatic castration-sensitive prostate cancer (nmCSPC) or each section of the stages. Serum CCL2′s usefulness was investigated as a prognostic nmCSPC biomarker in this study. Methods: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital from 2007 to 2013. A total of 230 patients with nmCSPC were included in this study of the 255 patients with histologically diagnosed prostate cancer. The serum CCL2 efficacy as a prognostic nmCSPC biomarker was investigated retrospectively. Results: An independent significant predictor of worse OS was CCL2 ≥ 280 pg/dL and CRP ≥ 0.5 mg/dL in multivariate analysis. Gleason score ≥ 8 and CCL2 ≥ 280 pg/dL were independent significant predictors of CRPC-free survival (CFS) worsening in multivariate analysis. Serum CCL2 was a predictive biomarker for OS and CFS in nmCSPC. Furthermore, CCL2 ≥ 280 pg/mL patients had significantly worse visceral metastasis-free survival than those with CCL2 < 280 pg/mL. Conclusion: This study is the first to demonstrate serum CCL2 utility as a biomarker to predict OS and CFS in nmCSPC.
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Goyal, Lipika, Hui Zheng, Thomas Adam Abrams, Rebecca A. Miksad, Andrea J. Bullock, Jill N. Allen, Matthew B. Yurgelun, et al. "A phase 2 and biomarker study of sorafenib combined with FOLFOX in patients with advanced hepatocellular carcinoma (HCC)." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 270. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.270.
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270 Background: Sorafenib is the standard first line treatment for advanced HCC and showed a median time to progression (TTP) of 5.5 months and an overall response rate (ORR) of 2% in the phase III SHARP trial. FOLFOX has shown modest activity in HCC with a progression free survival (PFS) of 2.9 months and ORR of 8% in a phase III trial. In this single-arm, multicenter phase 2 and biomarker study, sorafenib plus FOLFOX was evaluated in the first line treatment of advanced HCC. Methods: Patients with histologically proven advanced HCC, Child Pugh A liver function, and no prior systemic therapies received sorafenib 400mg orally twice daily during a 2-week lead-in, followed by concurrent modified FOLFOX (5-FUCI 1200mg/m2/day for 46 hours and LV 400mg/m2 bolus, Oxaliplatin 85mg/m2) on day 1 and 15 of each 28-day cycle. The primary endpoint was TTP, calculated from date of study entry to date of radiological or clinical disease progression. Serial plasma anti-angiogenic and anti-inflammatory biomarkers were evaluated. Results: The study enrolled 40 patients with advanced HCC: median age, 65 years; male 85%; Child Pugh A5, 70%; BCLC stage C, 95%; HCC etiology, HCV 40%, HBV 13%, alcohol 13%. Grade 3/4 adverse events were notable for AST (23%), ALT (15%), bilirubin (10%), diarrhea (10%), anemia (10%), hypertension (5%), hand-foot syndrome (5%), and thrombocytopenia (5%). Dose reductions for sorafenib and FOLFOX were done in 73% and 65% of patients, respectively. The median TTP was 8.8 months (95%CI, 6.5-11.2). The ORR was 18%, and the stable disease rate was 55%. Among 36 patients with a baseline AFP ≥ 5 ng/mL, 10 (28%) had a ≥ 50% drop in AFP. Low baseline plasma levels of sVEGFR1, VEGF-C, and bFGF and high levels of s-cMET and IL-12 tended to associate with longer TTP (p < 0.10). Decreased s-cMET at day 15 and decreased s-cMET and IL-2 at day 43 were associated with longer TTP (p < 0.05). Conclusions: Sorafenib+FOLFOX demonstrated encouraging clinical efficacy with moderate toxicity in the first line treatment of advanced HCC. Initial biomarker evaluation suggested a correlation between TTP and baseline angiogenic markers as well as changes in IL-2 and s-cMET. Complete biomarker analysis will be presented at the meeting. Clinical trial information: NCT01775501.
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Cecchi, Fabiola, Daniel V. T. Catenacci, Yuan Tian, Rosalba Miceli, Filippo Pietrantonio, Alessandro Pellegrinelli, Antonia Martinetti, Maria Di Bartolomeo, and Todd A. Hembrough. "Quantitative proteomic analysis of TUBB3 to identify gastric cancer patients who may benefit from docetaxel: A reevaluation of the ITACA-S trial." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 59. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.59.
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59 Background: Chemotherapy (CTX) becomes targeted therapy when biomarkers can predict a patient’s response. A relationship between resistance to taxanes and overexpression of class III b-tubulin (TUBB3) has been suggested by small clinical studies, but not confirmed in randomized trials. The Intergroup Trial of Adjuvant CTX in Adenocarcinoma of the Stomach (ITACA-S) evaluated the survival advantage of postoperative sequential CTX with FOLFIRI followed by docetaxel plus cisplatin in comparison to monotherapy with 5-FU/LV in patients with radically resected gastric cancer (N = 1106). The results showed no difference in survival between the two CTX arms. In a random subset of patients (N = 247) from the ITACA-S trial, we applied mass spectrometry-based proteomics to assess the role of TUBB3 as a predictive biomarker for response to taxane-containing therapy. Methods: Archived tumor tissues were microdissected and solubilized for proteomic analysis. TUBB3 and 44 other protein biomarkers were quantified using a mass spectrometry-based selected reaction monitoring assay. A predetermined TUBB3 cutoff of 700 amol/µg was based on the assay’s limit of detection. The Mantel-Cox log-rank test was used for survival comparisons. Results: Among patients treated with taxane-containing CTX (n = 125), those with TUBB3 levels below the cutoff had nearly twice the median overall survival (OS) as patients with TUBB3 levels above the cutoff (1566 vs. 801 days, p = 0.0282). TUBB3 levels made no statistical difference in survival among patients who did not receive taxane. Of note, among patients with high TUBB3 levels ( > 700 amol), those treated without taxane-containing CTX survived far longer than patients in the taxane arm (OS = 1991 vs 801 days, p = 0.048). Conclusions: Quantitative proteomic analysis of TUBB3 expression identified a subset of gastric cancer patients who benefitted from the addition of docetaxel to adjuvant CTX. Patients with high TUBB3 expression levels had worse outcomes on a taxane-containing regimen than on CTX without taxane. Personalized CTX based on the TUBB3 biomarker is promising and warrants further validation. Clinical trial information: NCT01989858.
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Tan, Wan Ying, Melissa Tian, Nensi Ruzgar, Astrid Hengartner, Bethsebie Sailo, Olivia Ang-Olson, Airol Ubas, et al. "Use of distinct molecular signatures of appendiceal cancer subtypes to assess biomarker development." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 189. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.189.
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189 Background: Appendiceal Neoplasms are diverse entities which have a variety of clinical presentations, histologic subtypes, biologic behavior, and patient outcomes. Advanced disease at initial diagnosis is not uncommon and therapeutic options are limited. This study aims to identify potential targets to develop epigenetics-based therapeutics/biomarkers. Methods: Archival (FFPE) specimens were collected from 25 patients with histologically confirmed and subtyped appendiceal neoplasia and 16 age-matched non-neoplastic controls. Four appendiceal neoplastic processes identified: Low grade appendiceal neoplasm (LAMN), pseudomyxoma peritonei (intra-peritoneal spread of LAMN), conventional-type adenocarcinoma and goblet cell adenocarcinoma. Gene expression profiling was performed using the HTG EdgeSeq Oncology Biomarker panel. Differentially expressed genes (DEGs) were selected with cut-off threshold FDR<0.05 and analyzed using Qlucore Explorer and functional analyses via Ingenuity Pathway Analysis (IPA). Results: Four appendiceal neoplastic processes identified: pseudomyxoma peritonei (20%), low-grade appendiceal mucinous neoplasm (24%), adenocarcinoma (24%), and goblet cell adenocarcinoma (32%). Unsupervised hierarchical clustering identified 498 DEGs (424 up, 74 down) between all appendiceal cancer versus age-matched controls that showed enrichment in B-cell inflammatory signaling, senescence, cell cycle regulation, PI3K/AKT signaling, cell cycle checkpoint control pathways, and sets relating to NANOG in stem cell pluripotency (all p0.001). G1/S checkpoint, apoptosis, ATM, and PTEN signaling are downregulated (p0.001). TP53, E2F1, IL6, IFNG, TNF, and HGF (p0.001) regulated overlapping genes. Four-subgroups comparison found 67 DEGs involved in T-helper cell differentiation, immune-mediated apoptosis, T-cell fatigue, and PD1/PDL1 signaling to be dysregulated (p0.001). IFNG, FGF2, POU5F1, TNF, and MYC (p0.001) were upstream regulators. Conclusions: In this study, downregulated gene expressions in appendiceal cancers are related to cell proliferation and death control mechanisms, with a trend towards overexpression of inflammatory and cell cycle pathways. It is postulated that genes involved in these pathways are hypermethylated. More research is being undertaken on epigenetics-based biomarkers for diagnosis and prognosis. Given PI’s decades of experience in biomarker research, we aim to develop a "single blood test" to expand bedside monitoring alternatives that align with the National Cancer Moonshot Initiative to discover cancer early, when the likelihood of a cure is highest.
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Yip, Sonia, Rozelle Harvie, Andrew James Martin, Katrin Marie Sjoquist, Eric Tsobanis, Yoon-Koo Kang, Yung-Jue Bang, et al. "Evaluation of circulating VEGF based biomarkers in INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG)." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 64. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.64.
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64 Background: The INTEGRATE study evaluated activity of regorafinib (REG) v placebo (PBO) in 147 eligible patients with refractory AOGC. REG was highly effective in prolonging progression free survival (PFS). Differences between regions (i.e. Australia New Zealand/Canada (ANZ/CAN) vs Korea) were found in the magnitude of effect, but REG was effective across all regions and subgroups. We report on an exploratory analysis of VEGF biomarkers to identify predictive/prognostic markers. Methods: Protein biomarkers IL8, VEGF-A,-B,-C-D, soluble(s)VEGFR-1,-2-3 were analysed in plasma at baseline (BL) by multiplex immunoassays (Bio-Plex,BioRad) or ELISA (Abnova). Spearman statistics were used to quantify correlations between markers. Wilcoxon Rank-Sum tests were used to compare markers across regions. The prognostic and predictive value of markers was determined using cox proportional hazards analysis of PFS. Results: There were moderate-to-strong correlations between BL levels of IL8 and VEGF-C (ρ = 0.68), IL8 and VEGF-D (ρ = 0.66), VEGF-A and VEGF-C (ρ = 0.68), VEGF-A and sVEGFR-1 (ρ = 0.54); and a modest negative correlation between VEGF-D and sVEGRF-1 (ρ = -0.33). The regions differed according to BL levels of: VEGF-A (higher in ANZ/CAN; p = 0.0015), VEGF-B (higher in Korea; p = 0.0003), VEGF-D (higher in Korea; p <.0001), and sVEGFR-1 (higher in ANZ/CAN; p <.0001). Adjusting for treatment group, there were statistically significant negative associations between PFS and BL IL8 (p = 0.047), VEGF-A (p = 0.037) and sVEGFR-1 (p = 0.045). There was no convincing statistical evidence that any BL plasma biomarker modified the effect of REG. The effect of region on effectiveness of REG was maintained when evaluated in conjunction with BL biomarkers individually and in combination. Conclusions: Highplasma IL8, VEGF-A and sVEGFR-1 may be adverse prognostic factors. A predictive VEGF blood based biomarker remains elusive. A broader biomarker study including markers beyond the VEGF axis and tissue based markers is ongoing. Clinical trial information: ACTRN12612000239864.
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Angelini, Dana, and Alok Khorana. "Risk Assessment Scores for Cancer-Associated Venous Thromboembolic Disease." Seminars in Thrombosis and Hemostasis 43, no. 05 (March 6, 2017): 469–78. http://dx.doi.org/10.1055/s-0036-1597281.
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AbstractCurrent guidelines recommend that patients with cancer be assessed for venous thromboembolism (VTE) risk at the time of chemotherapy initiation and periodically thereafter. Rates of VTE vary substantially among cancer patients. Multiple clinical factors contribute to VTE risk, including the primary site of cancer, extent of disease, interventions including major surgery, hospitalization, and systemic therapy. However, risk of VTE cannot reliably be predicted based on a single risk factor or biomarker. Within the last decade, risk assessment scores have been developed in cancer patients to more reliably predict thromboembolic events. This review provides an overview of evidence supporting the use of such tools for both primary and recurrent cancer-associated VTE. Potential applications of risk assessment tools as well as current knowledge gaps are outlined.
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Brown-Glaberman, Ursa, Marilyn Marron, Pavani Chalasani, Robert Livingston, Maria Iannone, Jennifer Specht, and Alison T. Stopeck. "Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer." Disease Markers 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/9810383.
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Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients.Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy.Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p=0.02) but not AC (p=0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy.Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.
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Parikh, Purvish M., Gouri Shankar Bhattacharyya, Ghanshyam Biswas, Arvind Krishnamurty, Dinesh Doval, Anil Heroor, Sanjay Sharma, et al. "Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India." South Asian Journal of Cancer 10, no. 04 (December 2021): 213–19. http://dx.doi.org/10.1055/s-0041-1742080.
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AbstractBreast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.
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Cai, Yuping, Nicholas J. W. Rattray, Qian Zhang, Varvara Mironova, Alvaro Santos-Neto, Engjel Muca, Ana K. Rosen Vollmar, et al. "Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage." Metabolites 10, no. 6 (June 19, 2020): 257. http://dx.doi.org/10.3390/metabo10060257.
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The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, p < 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670–0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens.
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Nishioka, M., M. Shimada, N. Kurita, T. Iwata, S. Morimoto, K. Yoshikawa, J. Higashijima, T. Miyatani, H. Kashihara, and C. Mikami. "A randomized phase II trial of chemoradiotherapy with oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase for low rectal cancer: An interim report." Journal of Clinical Oncology 29, no. 4_suppl (February 1, 2011): 524. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.524.
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524 Background: Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. In ASCO 2008 Gastrointestinal Cancers Symposium, we reported that the patients with up-regulation of 17 genes were suggested to be good responder of CRT. Our purpose of this study was to evaluate the toxicity and efficacy of CRT using UFT versus S-1 and explore biomarkers for response in patients with locally advanced rectal cancer. Methods: Fifty patients who received preoperative CRT (40Gy radiotherapy) were randomly assigned to either UFT or S-1. UFT and S-1 were administered during the radiotherapy course. S-1 was a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase and had potent radiosensitizing property. Biopsy specimens were obtained from rectal cancer before preoperative CRT and were analyzed by focused DNA microarray (132 genes). To pick up the predictive factors, the 132 genes were selected in the view of sensitivity of 5FU. Response to CRT was determined by RECIST and histopathologic examination of surgically resected specimens and classified as responders (CR, PR and grade 2, 3) or nonresponders (SD, PD and grade 0, 1). Results: UFT group (n=25) and S-1 group (n=25) were enrolled. Response rate (grade 2 or 3) to CRT determined by histopathologic examination of surgically resected specimens was 58% in the UFT group and was 75% in the S-1 group. Response rate evaluated by RECIST criteria was 62% in the UFT group and was 77% in the S-1 group. National Cancer Institute Common Toxicity Criteria grade 2 or 3 toxicity was observed in 8% of the patients in the UFT group and 23% of patients in the S-1 group. Grade 2 or 3 toxicity in the UFT group was neutropenia and was diarrhea, neutropenia and dermatitis in the S-1 group. In ASCO 2010, we will report each candidate biomarker genes for response to CRT in the UFT and S-1 group. Conclusions: The results have suggested that CRT using UFT or S-1 is feasible and effective for patients with locally advanced rectal cancer. [Table: see text]
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Kar, Ketaki, Suman Ghosh, and Anup Kumar Roy. "A Study of CD44 Positive Cancer Cells in Epithelial Ovarian Cancer and their Correlation with P53 And Ki67." Journal of Laboratory Physicians 13, no. 01 (February 22, 2021): 050–57. http://dx.doi.org/10.1055/s-0041-1724235.
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Abstract Context Epithelial ovarian carcinomas are one of the most common lethal gynecological malignancies. There is no specific symptom or biomarker for detection of this malignancy in early stage. So, the advanced stage, nature of frequent recurrences, and resistance to chemotherapies make it very difficult to deliver proper treatment to patients. Efforts are on to identify the presence of cancer stem cell by using a specific biomarker in epithelial ovarian cancer in the early stage. Objectives This study aims to identify the CD44 positive cancer cells in epithelial ovarian carcinoma of different histopathological types. It also intends to correlate the expression of CD44 with the expression of p53 and Ki67. Materials and Methods Sections from diagnosed specimens of ovarian epithelial neoplasm had been fixed in 10% formalin and embedded in paraffin, and they were used for immunohistochemical (IHC) staining for CD44, p53, and Ki67, using a peroxidase kit with mouse monoclonal antibodies. Then, the slides were evaluated for both tumor cell percentage and intensity of immunoreactivity. Statistical Analysis Chi-square had been used to find the significance of study. Significance level was considered at p value < 0.05 Results In this study, 40 patients were included in a period of one and a half years. The present study suggested that the levels of CD44 expression were increased in epithelial ovarian cancer compared to borderline tumor. CD44 was positively correlated with the ki67 expression and tumor grade. High-grade serous, mucinous, and endometrioid tumors were associated with high CD44 expression. Positivity of CD44 was found significantly higher in case of positive status of p53 (z = 3.65; p < 0.0001). Conclusion We can correlate CD44 positive cancer stem cells with grade of ovarian carcinomas, but for prognostic significance and therapeutic applications, more corroborative and multicentric works in this field are needed. CD44 can be targeted for therapy in recurrent and resistant cases of ovarian cancer.
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Harbin, Laura M., Holly H. Gallion, Derek B. Allison, and Jill M. Kolesar. "Next Generation Sequencing and Molecular Biomarkers in Ovarian Cancer—An Opportunity for Targeted Therapy." Diagnostics 12, no. 4 (March 29, 2022): 842. http://dx.doi.org/10.3390/diagnostics12040842.
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Ovarian cancer is the deadliest of all gynecologic malignancies claiming the lives of nearly 14,000 women in the United States annually. Despite therapeutic advances, the ovarian cancer mortality rate has remained stagnant since the 1980’s. The molecular heterogeneity of ovarian cancers suggest they may be more effectively treated via precision medicine. Current guidelines recommend germline and somatic testing for all new epithelial ovarian cancer diagnoses to assist providers in identifying candidates for targeted therapies. Next generation sequencing (NGS) identifies targetable, driver, and novel mutations used to guide treatment decisions. Performing NGS is standard of care in many other malignancies, but for ovarian cancer the use of NGS in daily practice is still emerging. This review discusses the targetable genetic mutations and role of NGS and molecular biomarker testing in the treatment of ovarian cancer.
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Vujicic, Ivo, Aleksandar Rusevski, Oliver Stankov, Zivko Popov, Aleksandar Dimovski, and Katarina Davalieva. "Potential Role of Seven Proteomics Tissue Biomarkers for Diagnosis and Prognosis of Prostate Cancer in Urine." Diagnostics 12, no. 12 (December 16, 2022): 3184. http://dx.doi.org/10.3390/diagnostics12123184.
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As the currently available tests for the clinical management of prostate cancer (PCa) are still far from providing precise diagnosis and risk stratification, the identification of new molecular marker(s) remains a pertinent clinical need. Candidate PCa biomarkers from the published proteomic comparative studies of prostate tissue (2002–2020) were collected and systematically evaluated. AZGP1, MDH2, FABP5, ENO1, GSTP1, GSTM2, and EZR were chosen for further evaluation in the urine of 85 PCa patients and controls using ELISA. Statistically significant differences in protein levels between PCa and BPH showed FABP5 (p = 0.019) and ENO1 (p = 0.015). A biomarker panel based on the combination of FABP5, ENO1, and PSA provided the highest accuracy (AUC = 0.795) for PCa detection. The combination of FABP5, EZR, AZGP1, and MDH2 showed AUC = 0.889 in PCa prognosis, with 85.29% of the samples correctly classified into low and high Gleason score (GS) groups. The addition of PSA to the panel slightly increased the AUC to 0.914. AZGP1, FABP5, and EZR showed significant correlation with GS, stage, and percentage of positive biopsy cores. Although validation using larger patient cohorts will be necessary to establish the credibility of the proposed biomarker panels in a clinical context, this study opens a way for the further testing of more high-quality proteomics biomarkers, which could ultimately add value to the clinical management of PCa.