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1
Kushwaha, Prem Prakash, Shiv Verma, and Sanjay Gupta. "Aquaporins as Prognostic Biomarker in Prostate Cancer." Cancers 15, no. 2 (January 4, 2023): 331. http://dx.doi.org/10.3390/cancers15020331.
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Prostate cancer is a complex heterogeneous disease that affects millions of males worldwide. Despite rapid advances in molecular biology and innovation in technology, few biomarkers have been forthcoming in prostate cancer. The currently available biomarkers for the prognosis of prostate cancer are inadequate and face challenges, thus having limited clinical utility. To date, there are a number of prognostic and predictive biomarkers identified for prostate cancer but lack specificity and sensitivity to guide clinical decision making. There is still tremendous scope for specific biomarkers to understand the natural history and complex biology of this heterogeneous disease, and to identify early treatment responses. Accumulative studies indicate that aquaporins (AQPs) a family of membrane water channels may serve as a prognostic biomarker for prostate cancer in monitoring disease advancement. In the present review, we discuss the existing prostate cancer biomarkers, their limitations, and aquaporins as a prospective biomarker of prognostic significance in prostate cancer.
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Emami, Nashmil, and Eleftherios P. Diamandis. "Utility of Kallikrein-Related Peptidases (KLKs) as Cancer Biomarkers." Clinical Chemistry 54, no. 10 (October 1, 2008): 1600–1607. http://dx.doi.org/10.1373/clinchem.2008.105189.
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Abstract Background: The human kallikrein-related peptidase (KLK) family consists of 15 highly conserved serine proteases, which are encoded by the largest uninterrupted cluster of protease genes in the human genome. To date, several members of the family have been reported as potential cancer biomarkers. Although primarily known for their biomarker value in prostate, ovarian, and breast cancers, more recent data suggest analogous roles of KLKs in several other cancers, including gastrointestinal, head and neck, lung, and brain malignancies. Among the proposed KLK cancer biomarkers, prostate-specific antigen (also known as KLK3) is the most widely recognized member in urologic oncology. Content: Despite substantial progress in the understanding of the biomarker utility of individual KLKs, the current challenge lies in devising biomarker panels to increase the accuracy of prognosis, prediction of therapy, and diagnosis. To date, multiparametric KLK panels have been proposed for prostate, ovarian, and lung cancers. In addition to their biomarker utility, emerging evidence has revealed a number of critical functional roles for KLKs in the pathogenesis of cancer and their potential use as therapeutic targets. Summary: KLKs have biomarker utility in many cancer types but individually lack sufficient specificity or sensitivity to be used in clinical practice; however, groups of KLKs and other candidate biomarkers may offer improved performance.
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Wu, Jui-Chuang, and Guang-Jer Wu. "METCAM Is a Potential Biomarker for Predicting the Malignant Propensity of and as a Therapeutic Target for Prostate Cancer." Biomedicines 11, no. 1 (January 13, 2023): 205. http://dx.doi.org/10.3390/biomedicines11010205.
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Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have been suggested for predicting malignant prostatic carcinoma cancer; however, only a few, such as PSA (prostate-specific antigen), Prostate Health Index (PHI), and PCA3, have been approved by the FDA. However, each biomarker has its merits as well as shortcomings. The serum PSA test is incapable of differentiating prostate cancer from BPH and also has an about 25% false-positive prediction rate for the malignant status of cancer. The PHI test has the potential to replace the PSA test for the discrimination of BPH from prostate cancer and for the prediction of high-grade cancer avoiding unnecessary biopsies; however, the free form of PSA is unstable and expensive. PCA3 is not associated with locally advanced disease and is limited in terms of its prediction of aggressive cancer. Currently, several urine biomarkers have shown high potential in terms of being used to replace circulating biomarkers, which require a more invasive method of sample collection, such as via serum. Currently, the combined multiple tumor biomarkers may turn out to be a major trend in the diagnosis and assessment of the treatment effectiveness of prostate cancer. Thus, there is still a need to search for more novel biomarkers to develop a perfect cocktail, which consists of multiple biomarkers, in order to predict malignant prostate cancer and follow the efficacy of the treatment. We have discovered that METCAM, a cell adhesion molecule in the Ig-like superfamily, has great potential regarding its use as a biomarker for differentiating prostate cancer from BPH, predicting the malignant propensity of prostate cancer at the early premalignant stage, and differentiating indolent prostate cancers from aggressive cancers. Since METCAM has also been shown to be able to initiate the spread of prostate cancer cell lines to multiple organs, we suggest that it may be used as a therapeutic target for the clinical treatment of patients with malignant prostate cancer.
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Fox, Natalie S., Emilie Lalonde, Julie Livingstone, Julia Hopkins, Yu-Jia Shiah, Vincent Huang, Takafumi Yamaguchi, et al. "Integrated somatic subtypes of localized intermediate-risk prostate cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): e560-e560. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.e560.
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e560 Background: Approximately two thirds of intermediate risk prostate cancer patients are over- or under- treated because we cannot correctly prognose this risk group; therefore we require novel biomarkers to better direct patient therapies and avoid subjecting patients to side effects without benefit. One reason genomic biomarkers are not currently used in clinical settings is because they are notoriously difficult to validate in follow-up studies. Furthermore, the lack of clear prostate cancer subtypes prevents the development of subtype specific biomarkers as is standard practice in breast cancer. We aim to improve biomarker validation rates by defining prostate cancer subtypes that can be used to create subtype specific biomarkers. Methods: First, we assess large scale genomic patterns using whole genome sequencing and methylation data and create integrative subtypes for intermediate risk prostate cancer. Second, we assess associations between specific aberrations and subtypes, and determine whether certain types of molecular aberrations are more important background aberrations for subtype specific biomarker development. Finally, we assess biases in prognostic performance of the published Lalonde biomarker between groups associated with patient subtypes to show that subtype aware biomarkers are necessary. Results: We demonstrate that the Lalonde biomarker is biased by the cohorts’ proportion of TMPRSS2-ERG (T2E) aberrations illustrating the need to develop different biomarkers for patients with T2E and patients without T2E. Further, we suggest integrative subtypes can be used to select patients with similar genomic profiles for biomarker analysis to improve biomarker validation rates. Conclusions: This analysis provides direct guidance for future biomarker development and addresses an important barrier to clinical use of genomic biomarkers for prostate cancer.
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Jakobsen, Niels Asger, Freddie Charles Hamdy, and Richard John Bryant. "Novel biomarkers for the detection of prostate cancer." Journal of Clinical Urology 9, no. 2_suppl (December 2016): 3–10. http://dx.doi.org/10.1177/2051415816656121.
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Prostate-specific antigen (PSA) is widely used as a biomarker in the detection of prostate cancer and for decision making regarding treatment options, response to therapy, and clinical follow-up. Despite its widespread use, it is well recognised that PSA has suboptimal performance as a screening tool due to poor specificity, resulting in high negative biopsy rates and potential ‘over-diagnosis’ and ‘over-treatment’ of clinically insignificant cancers. In particular, PSA does not reliably distinguish either cancer from benign prostatic conditions, or ‘clinically significant’ from ‘indolent cancers’, and it is inaccurate in predicting disease burden and response to treatment. There is an urgent demand for novel biomarkers to address these clinical needs. This article provides an update on the novel candidate biomarkers in development, which have shown potential for improving the detection of clinically significant cases of this malignancy.
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Bettin, Alfonso, Ismael Reyes, and Niradiz Reyes. "Gene Expression Profiling of Prostate Cancer–Associated Genes Identifies Fibromodulin as Potential Novel Biomarker for Prostate Cancer." International Journal of Biological Markers 31, no. 2 (April 2016): 153–62. http://dx.doi.org/10.5301/jbm.5000184.
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Background The aim of this study was to evaluate the gene expression profiles of a set of prostate cancer–associated genes in prostate cancer cell lines, to determine their association with different cancer phenotypes and identify potential novel biomarkers for this disease. Methods Quantitative real-time PCR was used to determine the expression profiles of 21 prostate cancer–associated genes in the human prostate cancer cell lines PC-3 and LNCaP, using the nontumorigenic cell line PWR-1E as control cell line. Genes evaluated were ESM-1, SERPINE2, CLU, BGN, A2M, PENK, FMOD, CD81, DCN, TSPAN8, KBTBD10, F2RL1, TMSB4X, SNCG, CXXC5, FOXQ1, PDPN, SPN, CAV1, CD24 and KLK3. A potential biomarker from this set of genes, the FMOD gene, encoding the small leucine-rich proteoglycan fibromodulin, was selected for further evaluation in clinical samples from patients diagnosed with benign or malignant prostatic disease. Results Several of the evaluated genes showed significantly altered expression in the prostate cancer cell lines, compared with nontumorigenic PWR-1E cells. Further evaluation of FMOD transcript in prostate clinical samples from patients diagnosed with benign or malignant prostatic disease identified a significant difference in the expression levels of this proteoglycan between benign and malignant tissue (p<0.05). Conclusions A number of gene transcripts were differentially expressed by the cell lines assayed. Among them, FMOD was further evaluated in clinical samples and was found to be differentially expressed between benign and prostate cancer tissue. Further validation of FMOD transcript in a larger population is required to ascertain its usefulness as biomarker for prostate cancer.
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Tosoian, Jeffrey, and Stacy Loeb. "PSA and Beyond: The Past, Present, and Future of Investigative Biomarkers for Prostate Cancer." Scientific World JOURNAL 10 (2010): 1919–31. http://dx.doi.org/10.1100/tsw.2010.182.
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The discovery of prostate-specific antigen (PSA) as a biomarker represented a major discovery in the early diagnosis and monitoring of prostate cancer. However, the use of PSA is limited by the lack of specificity and an inability to differentiate indolent from life-threatening disease reliably at the time of diagnosis. A multitude of studies have aimed to improve the performance of PSA as well as identify additional biomarkers. The purpose of this study is to review available data on prostate cancer biomarkers for prostate cancer screening and prognostication, including prostatic acid phosphatase, PSA, PSA derivatives (PSA density, free PSA, pro PSA, and PSA kinetics), PCA3, GSTP1, AMACR, and other newly emerging molecular and genetic markers.
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Barnett, Christine L., Scott A. Tomlins, Daniel J. Underwood, John T. Wei, Todd M. Morgan, James E. Montie, and Brian T. Denton. "Two-Stage Biomarker Protocols for Improving the Precision of Early Detection of Prostate Cancer." Medical Decision Making 37, no. 7 (March 31, 2017): 815–26. http://dx.doi.org/10.1177/0272989x17696996.
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Background. New cancer biomarkers are being discovered at a rapid pace; however, these tests vary in their predictive performance characteristics, and it is unclear how best to use them. Methods. We investigated 2-stage biomarker-based screening strategies in the context of prostate cancer using a partially observable Markov model to simulate patients’ progression through prostate cancer states to mortality from prostate cancer or other causes. Patients were screened every 2 years from ages 55 to 69. If the patient’s serum prostate-specific antigen (PSA) was over a specified threshold in the first stage, a second stage biomarker test was administered. We evaluated design characteristics for these 2-stage strategies using 7 newly discovered biomarkers as examples. Monte Carlo simulation was used to estimate the number of screening biopsies, prostate cancer deaths, and quality-adjusted life-years (QALYs) per 1000 men. Results. The all-cancer biomarkers significantly underperformed the high-grade cancer biomarkers in terms of QALYs. The screening strategy that used a PSA threshold of 2 ng/mL and a second biomarker test with high-grade sensitivity and specificity of 0.86 and 0.62, respectively, maximized QALYs. This strategy resulted in a prostate cancer death rate within 1% of using PSA alone with a threshold of 2 ng/mL, while reducing the number of biopsies by 20%. Sensitivity analysis suggests that the results are robust with respect to variation in model parameters. Conclusions. Two-stage biomarker screening strategies using new biomarkers with risk thresholds optimized for high-grade cancer detection may increase quality-adjusted survival and reduce unnecessary biopsies.
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Davalieva, Katarina, and Momir Polenakovic. "Proteomics in Diagnosis of Prostate Cancer/ Протеомика Во Дијагноза На Простатниот Карцином." PRILOZI 36, no. 1 (May 1, 2015): 5–36. http://dx.doi.org/10.1515/prilozi-2015-0027.
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Abstract Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa.
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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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Roychowdhury, Sameek, and Arul M. Chinnaiyan. "Advancing Precision Medicine for Prostate Cancer Through Genomics." Journal of Clinical Oncology 31, no. 15 (May 20, 2013): 1866–73. http://dx.doi.org/10.1200/jco.2012.45.3662.
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Prostate cancer is the most common type of cancer in men and the second leading cause of cancer death in men in the United States. The recent surge of high-throughput sequencing of cancer genomes has supported an expanding molecular classification of prostate cancer. Translation of these basic science studies into clinically valuable biomarkers for diagnosis and prognosis and biomarkers that are predictive for therapy is critical to the development of precision medicine in prostate cancer. We review potential applications aimed at improving screening specificity in prostate cancer and differentiating aggressive versus indolent prostate cancers. Furthermore, we review predictive biomarker candidates involving ETS gene rearrangements, PTEN inactivation, and androgen receptor signaling. These and other putative biomarkers may signify aberrant oncogene pathway activation and provide a rationale for matching patients with molecularly targeted therapies in clinical trials. Lastly, we advocate innovations for clinical trial design to incorporate tumor biopsy and molecular characterization to develop biomarkers and understand mechanisms of resistance.
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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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Liu, Qi, Jun Jian Ding, Fei Yi Liu, Zuo Zhen Jiang, Lin Li, Xin Bing Xiao, and Jie Zhen Wang. "The novel biomarkers in diagnosis of prostate cancer." Cancer Plus 1, no. 1 (March 22, 2019): 8. http://dx.doi.org/10.18063/cp.v1i1.233.
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The prostate specific antigen (PSA) as a biomarker for prostate cancer (PCa) diagnosis has been widely used in the clinic for several decades. However, PSA has a low specificity for PCa diagnosis, thereby several gene, blood and urine-based biomarkers (such as sarcosine) underlying biology of PCa progression are being developed to improve the accuracy of PCa diagnosis. In the present review, we focus on novel PCa biomarkers, which are ptentially superior to PSA in PCa screening and facilitate clinical PCa diagonosis. The early PCa screening with reliable biomarkers is critical in reducing the mortality of clinical PCa (high-risk PCa). For clinical insignificant PCa (low-risk PCa) patients and benign prostatic hyperplasia patients, biopsies should be avoided and disease progression should be monitored by using non-invasive biomarkers.
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Deluce, Jasna E., Luisa Cardenas, Aly-Khan Lalani, Saman Maleki Vareki, and Ricardo Fernandes. "Emerging Biomarker-Guided Therapies in Prostate Cancer." Current Oncology 29, no. 7 (July 18, 2022): 5054–76. http://dx.doi.org/10.3390/curroncol29070400.
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Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy.
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Uemura, Hiroji, Noriaki Arakawa, Yusuke Itoh, Takashi Kawahara, Yasuhide Miyoshi, Shouhei Akiba, and Norihisa Ohtake. "Novel biomarker of specific castration-resistant prostate cancer (CRPC) by exploring the proteome analysis." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 247. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.247.
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247 Background: It is well known that prostate specific antigen (PSA) level has no reliable correlation with pathological malignancy of prostate cancer and is not a predictor for the development of castration resistant prostate cancer (CRPC). The aim of this study is to explore novel biomarkers to predict the development of CRPC by using proteomics from secreted proteins from human prostate cancer cells. Methods: The proteins secreted from 6 prostate cancers in culture medium were analyzed and compared with 8 other cancer cells including renal and urothelial cancers using LTQ Orbitrap mass spectrometer. With the focus on high tissue specificity, the candidate biomarker proteins were then identified through analysis of gene expressions in proteins common to human prostate cancers by real time qPCR. Next, a system to measure the identified mouse monoclonal antibodies against the focused proteins was established. Finally, serum levels of these proteins from 33 patients with benign prostate hyperplasia (BPH), 31 with untreated prostate cancer (PCa) and 35 with CRPC, were measured. Results: The proteome analysis identified 12 candidates of secreted cell membrane proteins as new biomarkers. The proteome analysis indicated that not only matured GDF15, but pro-peptide as well as fragments (GDDP) are released from prostate cancer cells. Patients’ serum was analyzed for matured and pro-peptide GDF15 using ELISA and immunoprecipitation-MRM mass spectrometry. The results showed that the serum level of GDDP-1, one of the processing forms of GDDP, was significantly higher in CRPC than those in BPH and untreated PCa (P < 0.01). ROC analysis also showed that the AUC of GDDP-1(0.86) was higher than that of matured GDF15 (0.76). When the cutoff value of GDDP-1 was set at 4.0 ng/mL, there was a significant difference of overall survival (OS) in CRPC patients between those with more than 4.0 ng/mL compared to less than 4.0 ng/mL of GDDP-1, whereas there was no significant difference of OS measurable by PSA in CRPC patients. These data suggest that GDDP-1 may be a novel biomarker for CRPC. Conclusions: GDDP-1 shows potential as a novel biomarker for CRPC.
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Jefferies, Matthew T., Christopher S. Pope, Howard G. Kynaston, Alan R. Clarke, Richard M. Martin, and Josephine C. Adams. "Analysis of Fascin-1 in Relation to Gleason Risk Classification and Nuclear ETS-Related Gene Status of Human Prostate Carcinomas: An Immunohistochemical Study of Clinically Annotated Tumours From the Wales Cancer Bank." Biomarkers in Cancer 9 (January 1, 2017): 1179299X1771094. http://dx.doi.org/10.1177/1179299x17710944.
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Although prostate-specific antigen (PSA) testing can identify early-stage prostate cancers, additional biomarkers are needed for risk stratification. In one study, high levels of the actin-bundling protein, fascin-1, were correlated with lethal-phase, hormone-refractory prostate cancer. Analyses of independent samples are needed to establish the value of fascin-1 as a possible biomarker. We examined fascin-1 by immunohistochemistry in tumour specimens from the Wales Cancer Bank in comparison with nuclear-located ETS-related gene (ERG), an emerging marker for aggressive prostate cancer. Fascin-1 was elevated in focal areas of a minority of tumours, yet fascin-1-positivity did not differentiate tumours of low-, intermediate-, or high-risk Gleason scores and did not correlate with PSA status or biochemical relapse after surgery. Stromal fascin-1 correlated with high Gleason score. Nuclear ERG was upregulated in tumours but not in stroma. The complexities of fascin-1 status indicate that fascin-1 is unlikely to provide a suitable biomarker for prediction of aggressive prostate cancers.
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Barma, Nafisa, Timothy C. Stone, Lina Maria Carmona Echeverria, and Susan Heavey. "Exploring the Value of BRD9 as a Biomarker, Therapeutic Target and Co-Target in Prostate Cancer." Biomolecules 11, no. 12 (November 30, 2021): 1794. http://dx.doi.org/10.3390/biom11121794.
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Background and aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA M.expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression, and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signalling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.
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Alghezi, Dhafer, Rasha Aljawher, and Sada Musawi. "Increased CD73 expression is associated with poorly differentiated Gleason score and tumor size in prostate cancer." Journal of Advanced Biotechnology and Experimental Therapeutics 6, no. 1 (2023): 161. http://dx.doi.org/10.5455/jabet.2023.d115.
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There are few prostate cancer prognostic biomarkers. However, clinical difficulties in distinguishing between aggressive and non-aggressive tumors have been observed. CD73 is a 70-kDa glycosylphosphatidylinositol (GPI)-linked ecto-enzyme that reduces antitumor immunity in mouse models of tumor, particularly prostate cancer. It's believed to be a promising biomarker for predicting the clinical development and prognosis of certain tumor types. Its function in prostate cancer, however, is unknown. This study aims to investigate the hypothesis that CD73 may be used as a biomarker in prostate cancer diagnosis and/or prognosis. Nuclear and cytoplasmic CD73 staining has been evaluated by immunohistochemistry using benign (23) and malignant (75) prostate tissues. The immunohistochemical study showed nuclear and cytoplasmic CD73 staining in cancerous and non-cancerous prostate tissues. Increased CD73 staining was shown in prostate cancer tissues compared to benign prostate tissues. A negative association between CD73 expression and Gleason scores has been observed. However, increased cytoplasmic CD73 staining was significantly associated with increasing tumor size. This finding suggests that CD73 may have a role in cancer development or aggressiveness, indicating that more research is needed to better understand its function and determine whether it might be used as a diagnostic biomarker for prostate cancer.
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Iqbal, Safdar, Abdul Qadeer Saad, Aamal Haleem, Zahida Parveen, Imtiaz Hussain, Muhammad Kashif Qamar, and Muhammad Zahid. "Medically Important Novel Biomarkers Therapy for Targeting the Cancerous and Tumor Cells in Combating the Infectious Diseases." Saudi Journal of Pathology and Microbiology 6, no. 10 (October 27, 2021): 395–400. http://dx.doi.org/10.36348/sjpm.2021.v06i10.013.
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Cancer biomarkers are the biological molecules produced by the body or tumor in a person with cancer. In order to place the functioning of biomarkers for clinical investigating, they are passed through different clinical trials in order to check their treatment rate as compared to the normal markers. Different genes are involved in causing the breast cancer and early diagnosis through biomarkers provides an effective way to control the mutations caused in cancerous tissues. Genetic biomarkers are those biological molecules that can detect the change in the DNA and RNA structures. HER2 somatic mutations lead to increase in progressions of cancer development non-small cell lung cancers as well as in breast cells. The most important biomarkers are ALF-alpha-fetoprotein is a protein that in humans is encoded by the AFP gene in the liver. Mutational defect in AFP gene leads to severe damage to liver. C-reactive protein (CRP) is the biomarker for inflammation in the body cells. Prostate specific antigen (PSA) is the biomarker used for detection of prostate cancer. Microsatellite instability analysis of a tumor which provides predictive and also prognostic information. Cerebrospinal fluid (CSF) is the important biomarker for the diagnosis of dementia, Alzheimer’s disease pathologies.
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Mucci, Lorelei A., Thomas Ahearn, Kathryn Penney, Andreas Pettersson, Rebecca E. Graff, Philip W. Kantoff, Stephen Finn, and Massimo Loda. "Precision prevention of TMPRSS2:ERG prostate cancer." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 78. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.78.
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78 Background: Increased integration of tumor biomarker data into prostate cancer epidemiology studies is needed to identify molecular subtypes that underlie its etiology and progression. We hypothesize that the TMPRSS2:ERG gene fusion is a unique prostate cancer subtype that is etiologically distinct from cancers lacking TMPRSS2:ERG. Methods: We leveraged the Physicians’ Health Study and Health Professionals Follow-up Study cohort data on pre- and post-diagnostic lifestyle factors, inherited genetic variants, circulating biomarkers, and clinical data and follow-up for 30 years. We have a tumor repository of men with prostate cancer and tumor tissue microarrays. Using immunohistochemistry, we characterized TMPRSS2:ERG status for 1,491 incident prostate cancer cases in these cohorts, and also have biomarker data on a range of additional markers from immunohistochemistry and mRNA expression profiling. Results: Fifty percent of prostate cancer cases were ERG-positive. ERG-positive cancers show much higher expression of insulin/IGF signaling, PTEN loss, higher VDR expression, as well as expression of mismatch repair genes. In contrast, ERG-negative prostate cancer is characterized by increased presence of chronic inflammation and atrophy. We found higher pre-diagnostic free testosterone levels, but not other sex hormones, were associated with increased risk of ERG-positive (OR = 1.4, 95% CI = 1.0-1.8) but not ERG-negative disease (OR = 0.9, 95% CI = 0.7-1.2). Of 39 known genetic risk loci, six were significantly associated (p < 0.05) with ERG+ versus ERG- cancer (2 expected by chance). Prostate cancer risk factors such as taller height (an indicator of growth factors in puberty) are uniquely associated with ERG-positive prostate cancer. Moreover, we observe a complex interaction of components of insulin/IGF and ERG-status on prostate cancer mortality. Conclusions: TMPRSS2:ERG is a highly prevalent somatic event in prostate cancer that likely defines a unique molecular subtype of this common disease. Understanding the differences between these two prostate cancer subtypes may enhance opportunities for prevention.
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Takakura, Michiko, Akira Yokomizo, Yoshinori Tanaka, Michimoto Kobayashi, Giman Jung, Miho Banno, Tomohiro Sakuma, et al. "Carbonic Anhydrase I as a New Plasma Biomarker for Prostate Cancer." ISRN Oncology 2012 (November 19, 2012): 1–10. http://dx.doi.org/10.5402/2012/768190.
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Serum prostate-specific antigen (PSA) levels ranging from 4 to 10 ng/mL is considered a diagnostic gray zone for detecting prostate cancer because biopsies reveal no evidence of cancer in 75% of these subjects. Our goal was to discover a new highly specific biomarker for prostate cancer by analyzing plasma proteins using a proteomic technique. Enriched plasma proteins from 25 prostate cancer patients and 15 healthy controls were analyzed using a label-free quantitative shotgun proteomics platform called 2DICAL (2-dimensional image converted analysis of liquid chromatography and mass spectrometry) and candidate biomarkers were searched. Among the 40,678 identified mass spectrum (MS) peaks, 117 peaks significantly differed between prostate cancer patients and healthy controls. Ten peaks matched carbonic anhydrase I (CAI) by tandem MS. Independent immunological assays revealed that plasma CAI levels in 54 prostate cancer patients were significantly higher than those in 60 healthy controls (, Mann-Whitney test). In the PSA gray-zone group, the discrimination rate of prostate cancer patients increased by considering plasma CAI levels. CAI can potentially serve as a valuable plasma biomarker and the combination of PSA and CAI may have great advantages for diagnosing prostate cancer in patients with gray-zone PSA level.
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Kohli, Manish, Rui Qin, Rafael Jimenez, and Scott M. Dehm. "Biomarker-Based Targeting of the Androgen-Androgen Receptor Axis in Advanced Prostate Cancer." Advances in Urology 2012 (2012): 1–14. http://dx.doi.org/10.1155/2012/781459.
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Recent therapeutic advances for managing advanced prostate cancer include the successful targeting of the androgen-AR axis with several new drugs in castrate resistant prostate cancer including abiraterone acetate and enzalutamide (MDV3100). This translational progress from “bench to bed-side” has resulted in an enlarging repertoire of novel and traditional drug choices now available for use in advanced prostate cancer therapeutics, which has had a positive clinical impact in prolonging longevity and quality of life of advanced prostate cancer patients. In order to further the clinical utility of these drugs, development of predictive biomarkers guiding individual therapeutic choices remains an ongoing challenge. This paper will summarize the potential in developing predictive biomarkers based on the pathophysiology of the androgen-AR axis in tumor tissue from patients with advanced prostate cancer as well as inherited variation in the patient’s genome. Specific examples of rational clinical trial designs incorporating potential predictive biomarkers from these pathways will illustrate several aspects of pharmacogenetic and pharmacogenomic predictive biomarker development in advanced prostate cancer therapeutics.
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Aidoo-Brown, Josephine, Despina Moschou, and Pedro Estrela. "Multiplexed Prostate Cancer Companion Diagnostic Devices." Sensors 21, no. 15 (July 24, 2021): 5023. http://dx.doi.org/10.3390/s21155023.
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Prostate cancer (PCa) remains one of the most prominent forms of cancer for men. Since the early 1990s, Prostate-Specific Antigen (PSA) has been a commonly recognized PCa-associated protein biomarker. However, PSA testing has been shown to lack in specificity and sensitivity when needed to diagnose, monitor and/or treat PCa patients successfully. One enhancement could include the simultaneous detection of multiple PCa-associated protein biomarkers alongside PSA, also known as multiplexing. If conventional methods such as the enzyme-linked immunosorbent assay (ELISA) are used, multiplexed detection of such protein biomarkers can result in an increase in the required sample volume, in the complexity of the analytical procedures, and in adding to the cost. Using companion diagnostic devices such as biosensors, which can be portable and cost-effective with multiplexing capacities, may address these limitations. This review explores recent research for multiplexed PCa protein biomarker detection using optical and electrochemical biosensor platforms. Some of the novel and potential serum-based PCa protein biomarkers will be discussed in this review. In addition, this review discusses the importance of converting research protocols into multiplex point-of-care testing (xPOCT) devices to be used in near-patient settings, providing a more personalized approach to PCa patients’ diagnostic, surveillance and treatment management.
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Diamandis, Eleftherios P. "Early Prostate Cancer Antigen-2: A Controversial Prostate Cancer Biomarker?" Clinical Chemistry 56, no. 4 (April 1, 2010): 542–44. http://dx.doi.org/10.1373/clinchem.2009.140061.
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Gennaro, Kyle, Kristin Porter, Jennifer Gordetsky, Samuel Galgano, and Soroush Rais-Bahrami. "Imaging as a Personalized Biomarker for Prostate Cancer Risk Stratification." Diagnostics 8, no. 4 (November 30, 2018): 80. http://dx.doi.org/10.3390/diagnostics8040080.
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Biomarkers provide objective data to guide clinicians in disease management. Prostate-specific antigen serves as a biomarker for screening of prostate cancer but has come under scrutiny for detection of clinically indolent disease. Multiple imaging techniques demonstrate promising results for diagnosing, staging, and determining definitive management of prostate cancer. One such modality, multiparametric magnetic resonance imaging (mpMRI), detects more clinically significant disease while missing lower volume and clinically insignificant disease. It also provides valuable information regarding tumor characteristics such as location and extraprostatic extension to guide surgical planning. Information from mpMRI may also help patients avoid unnecessary biopsies in the future. It can also be incorporated into targeted biopsies as well as following patients on active surveillance. Other novel techniques have also been developed to detect metastatic disease with advantages over traditional computer tomography and magnetic resonance imaging, which primarily rely on defined size criteria. These new techniques take advantage of underlying biological changes in prostate cancer tissue to identify metastatic disease. The purpose of this review is to present literature on imaging as a personalized biomarker for prostate cancer risk stratification.
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Fredsøe, Jacob, Anne K. I. Rasmussen, Peter Mouritzen, Marianne T. Bjerre, Peter Østergren, Mikkel Fode, Michael Borre, and Karina D. Sørensen. "Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential." Diagnostics 10, no. 4 (March 28, 2020): 188. http://dx.doi.org/10.3390/diagnostics10040188.
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Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.
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Barani, Mahmood, Fakhara Sabir, Abbas Rahdar, Rabia Arshad, and George Z. Kyzas. "Nanotreatment and Nanodiagnosis of Prostate Cancer: Recent Updates." Nanomaterials 10, no. 9 (August 28, 2020): 1696. http://dx.doi.org/10.3390/nano10091696.
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The fabrication and development of nanomaterials for the treatment of prostate cancer have gained significant appraisal in recent years. Advancements in synthesis of organic and inorganic nanomaterials with charge, particle size, specified geometry, ligand attachment etc have resulted in greater biocompatibility and active targeting at cancer site. Despite all of the advances made over the years in discovering drugs, methods, and new biomarkers for cancer of the prostate (PCa), PCa remains one of the most troubling cancers among people. Early on, effective diagnosis is an essential part of treating prostate cancer. Prostate-specific antigen (PSA) or serum prostate-specific antigen is the best serum marker widely accessible for diagnosis of PCa. Numerous efforts have been made over the past decade to design new biosensor-based strategies for biomolecules detection and PSA miniaturization biomarkers. The growing nanotechnology is expected to have a significant effect in the immediate future on scientific research and healthcare. Nanotechnology is thus predicted to find a way to solve one of the most and long-standing problem, “early cancer detection”. For early diagnosis of PCa biomarkers, different nanoparticles with different approaches have been used. In this review, we provide a brief description of the latest achievements and advances in the use of nanoparticles for PCa biomarker diagnosis.
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Rezaei, Simin D., Joshua A. Hayward, Sam Norden, John Pedersen, John Mills, Anna C. Hearps, and Gilda Tachedjian. "HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer." Viruses 13, no. 3 (March 10, 2021): 449. http://dx.doi.org/10.3390/v13030449.
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Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV-E 4.1 (Pol and Env regions), HERV-H (Pol) and HERV-W (Gag) sequences in prostate cancer cells lines and normal prostate epithelial cells using qRT-PCR. HERV expression was also analysed in matched malignant and benign prostate tissue samples from men with prostate cancer (n = 27, median age 65.2 years (range 47–70)) and compared to prostate cancer-free male controls (n = 11). Prostate cancer epithelial cell lines exhibited a signature of HERV RNA overexpression, with all HERVs analysed, except HERV-E Pol, showing heightened expression in at least two, but more commonly all, cell lines analysed. Analysis of primary prostate material indicated increased expression of HERV-E Pol but decreased expression of HERV-E Env in both malignant and benign regions of the prostate in men with prostate cancer as compared to those without. Expression of HERV-K Gag was significantly higher in malignant regions of the prostate in men with prostate cancer as compared to matched benign regions and prostate cancer-free men (p < 0.001 for both), with 85.2% of prostate cancers donors showing malignancy-associated upregulation of HERV-K Gag RNA. HERV-K Gag protein was detected in 12/18 (66.7%) malignant tissues using immunohistochemistry, but only 1/18 (5.6%) benign tissue sections. Heightened expression of HERV-K Gag RNA and protein appears to be a sensitive and specific biomarker of prostate malignancy in this cohort of men with prostate carcinoma, supporting its potential utility as a non-invasive, adjunct clinical biomarker.
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Davey, Michelle, Sami Benzina, Marc Savoie, Guy Breault, Anirban Ghosh, and Rodney J. Ouellette. "Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study." International Journal of Molecular Sciences 21, no. 21 (November 6, 2020): 8330. http://dx.doi.org/10.3390/ijms21218330.
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Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.
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Munteanu, Vlad Cristian, Raluca Andrada Munteanu, Diana Gulei, Vlad Horia Schitcu, Bogdan Petrut, Ioana Berindan Neagoe, Patriciu Achimas Cadariu, and Ioan Coman. "PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer." Diagnostics 10, no. 10 (October 10, 2020): 806. http://dx.doi.org/10.3390/diagnostics10100806.
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Prostate cancer represents the most encountered urinary malignancy in males over 50 years old, and the second most diagnosed after lung cancer globally. Digital rectal examination and prostatic specific antigen were the long-time standard tools for diagnosis but with a significant risk of overdiagnosis and overtreatment. Magnetic resonance imaging recently entered the diagnosis process, but to this date, there is no specific biomarker that accurately indicates whether to proceed with the prostate biopsy. Research in this area has gone towards this direction, and recently, serum, urine, imagistic, tissue biomarkers, and Risk Calculators promise to help better diagnose and stratify prostate cancer. In order to eliminate the comorbidities that appear along with the diagnosis and treatment of this disease, there is a constant need to implement new diagnostic strategies. Important uro-oncology associations recommend the use of novel biomarkers in the grey area of prostate cancer, to better distinguish the next step in the diagnostic process. Although it is not that simple, they should be integrated according to the clinical policies, and it should be considered that statistical significance does not always equal clinical significance. In this review, we analyzed the contribution of prostate-specific antigen (PSA)-based biomarkers (PHI, PHID, 4Kscore, STHLM3), imagistic techniques (mp-MRI and mp-US), and combined tests in the early diagnosis process of localized prostate cancer.
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Saxby, Helen, Christos Mikropoulos, and Stergios Boussios. "An Update on the Prognostic and Predictive Serum Biomarkers in Metastatic Prostate Cancer." Diagnostics 10, no. 8 (July 31, 2020): 549. http://dx.doi.org/10.3390/diagnostics10080549.
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Serum biomarkers are molecules produced by normal and abnormal cells. Prostate specific antigen (PSA) is an example of a serum biomarker used widely in the diagnosis and prognostication of prostate cancer. PSA has its limitations as it is organ- but not cancer-specific. The aim of this review is to summarize the current published data on the potential prognostic and predictive biomarkers in metastatic prostate cancer (mPC) that can be used in conjunction with PSA. These biomarkers include microRNAs, androgen receptor variants, bone metabolism, neuroendocrine and metabolite biomarkers, and could guide treatment selection and sequence in an era where we strive to personalized therapy.
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Diamandis, Eleftherios P. "Prostate-specific Antigen: A Cancer Fighter and a Valuable Messenger?" Clinical Chemistry 46, no. 7 (July 1, 2000): 896–900. http://dx.doi.org/10.1093/clinchem/46.7.896.
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Abstract Background: Prostate-specific antigen (PSA) is a valuable prostatic cancer biomarker that is now widely used for population screening, diagnosis, and monitoring of patients with prostate cancer. Despite the voluminous literature on this biomarker, relatively few reports have addressed the issue of its physiological function and its connection to the pathogenesis and progression of prostate and other cancers. Approach: I here review literature dealing with PSA physiology and pathobiology and discuss reports that either suggest that PSA is a beneficial molecule with tumor suppressor activity or that PSA has deleterious effects in prostate, breast, and possibly other cancers. Content: The present scientific literature on PSA physiology and pathobiology is confusing. A group of reports have suggested that PSA may act as a tumor suppressor, a negative regulator of cell growth, and an apoptotic molecule, whereas others suggest that PSA may, through its chymotrypsin-like activity, promote tumor progression and metastasis. Summary: The physiological function of PSA is still not well understood. Because PSA is just one member of the human kallikrein gene family, it is possible that its biological functions are related to the activity of other related kallikreins. Only when the physiological functions of PSA and other kallikreins are elucidated will we be able to explain the currently apparently conflicting experimental data.
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Aboyan, I. A., E. N. Fedotova, S. I. Lemeshko, A. Yu Maksimov, and E. F. Komarova. "Tissue expression of the antiapoptotic protein survinin as a potential biomarker of prostate cancer." Cancer Urology 18, no. 2 (August 12, 2022): 58–65. http://dx.doi.org/10.17650/1726-9776-2022-18-2-58-65.
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Background. Excessive expression of survivin is associated with inhibition of cell death, activated by extrinsic or intrinsic apoptotic pathways. The survininin overexpression has been shown in various malignancies, including lung cancer, pancreatic and breast cancer, colon cancer, oral squamous cell carcinoma and high grade non-Hodgkin lymphomas.Aim. To investigate the level of survivin expression in prostate cancer tissues, and evaluate it as a diagnostic marker of prostate cancer.Materials and methods. The level of survivin expression and its subcellular localization were assessed immunohistochemically in patients with prostate cancer (n = 64) and benign prostatic hyperplasia (n = 33). Tissue samples obtained at transrectal biopsy were used for analysis. Prostate cancer samples obtained after cystprostatectomy in patients with normal prostate specific antigen level and normal ultrasound findings (n = 36) were considered control tissue (norm).Results. In prostate cancer group 3+ samples with a high level of survivin expression were present in 48.4 % of cases. In benign prostatic hyperplasia group the majority of samples were assessed as 2+, while 9.1 % of samples were negatively stained. 100 % of normal epithelium samples were negative. In patients with Gleason score <7 a survivin expression level was less than 3+ in 62.5 % of cases, and in patients with Gleason score >7 a highly positive reaction was detected in 68.8 % of cases. A high level of survivin expression was found in the large proportion of tissue samples at prostate specific antigen levels >10 ng/ml. Almost 50 % of highly positive cells were detected at a prostate health index (PHI) value of ≥60. The largest percentage of negative staining for surviving was common with PHI value <25. The degrees of staining for survining 1+ and 2+ prevailed in patients with prostate health index density (DPHI) <0.8, while a high level of prostate cells staining 3+ was observed at >0.8. As a Gleason score increase we observe the change of staining type for nucleocytoplasmic, and the largest number of samples has a staining degree of 2+ at a score GG4–5 (≥4 + 4). The type and frequency of prostate tissue samples staining were not differ depending on the initial prostate specific antigen level.Conclusion. Immunohistochemical assessment of the survivin level, including its subcellular localization, could be considered as tumor-associated and a potential biomarker for differential diagnosis and prediction of prostate cancer course.
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Świtońska, Milena, Oliwia A. Jarosz, Dagmara Szołna-Klufczyńska, and Katarzyna Sierakowska. "Medium Extracellular Vesicles—A Qualitative and Quantitative Biomarker of Prostate Cancer." Biomedicines 10, no. 11 (November 8, 2022): 2856. http://dx.doi.org/10.3390/biomedicines10112856.
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For years, the diagnosis of prostate cancer has been understated. Despite the relatively low mortality rate, prostate cancer is still one of the most common neoplasms in men, which proves the need for continuous improvements in the diagnostics of this disease. New biomarkers may address these challenges in the form of extracellular vesicles (EV) secreted by prostate cancer cells. The available literature in the PubMed, SCOPUS, and ResearchGate databases from the last ten years was analyzed using search phrases such as extracellular vesicles, microparticles, microvesicles, cancer biomarkers, and prostate cancer. Then, the research was selected in terms of the size of the tested EVs (the EV medium of 100–1000 nm diameter, was taken into account), the latest versions of the literature were selected and compiled, and their results were compared. The group of extracellular vesicles contain a substantial amount of genetic information that can be used in research on the specificity of prostate cancer and other cancers. So far, it has been shown that EVs produced by PCa cells express proteins specific for these cells, which, thanks to their specificity, can make EV useful biomarkers of prostate cancer. Moreover, the importance of the quantitative release of EV from PCa cells has been demonstrated, which may be necessary to diagnose prostate cancer malignancy. Each method positively correlates with Gleason’s results and is even characterized by greater diagnostic sensitivity. Medium extracellular vesicles are a promising research material, and their specificity and sensitivity may allow them to be used in future prostate cancer diagnostics as biomarkers.
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Nikitina, A. S., V. V. Babenko, K. A. Babalyan, A. O. Vasiliev, A. V. Govorov, E. A. Prilepskaya, S. A. Danilenko, O. V. Selezneva, and E. I. Sharova. "Primary candidate RNA biomarker screening by RNA-seq for prostate cancer diagnostics." Biomeditsinskaya Khimiya 61, no. 6 (2015): 781–84. http://dx.doi.org/10.18097/pbmc20156106781.
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The RNA-seq approach for prostate cancer candidate RNA biomarkers screening in plasma and urine obtained by minimally invasive or noninvasive methods is proved to be feasible. Significant amount of RNA biomarkers associated with prostate cancer according to the literature were found in plasma and urine samples obtained from patients with benign prostatic hyperplasia (BPH). The number of detected markers was shown to vary in accordance with method of library preparation used for transcriptome profiling. The detection of known RNA biomarkers for prostate cancer in urine and plasma samples shows the feasibility of such method for minimally invasive diagnostics. The fact of presence of the same RNA biomarkers in samples from patients with BPH suggests their possible lack of specificity and confirms the need for further research in this area.
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Rosa, Maria Inês da, Eduardo Ronconi Dondossola, Maria Cecilia Manenti Alexandre, Kristian Madeira, Florentino de Araújo Cardoso, and Antonio José Grande. "Urinary EN-2 to predict prostate cancer: Systematic review and meta-analysis." Revista da Associação Médica Brasileira 63, no. 7 (July 2017): 656–61. http://dx.doi.org/10.1590/1806-9282.63.07.656.
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Summary Introduction: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. Objective: To evaluate the accuracy of engrailed-2 protein (EN2) in urine as a prostate cancer biomarker. Method: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed), Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. Results: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75) and specificity was 89% (95CI 0.86-0.92). The DOR was 15.08 (95CI 8.43-26.97). Conclusion: The EN2 test showed high specificity (89%) and low sensitivity (66%).
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Canat, Lütfi, Hasan A. Atalay, Osman Can, İlter Alkan, and Alper Ötünçtemur. "Serum procalcitonin levels in prostate cancer: A new biomarker?" Urologia Journal 85, no. 2 (March 23, 2018): 46–50. http://dx.doi.org/10.1177/0391560317752600.
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Background: To examine the role of serum procalcitonin as a biomarker for the detection of prostate cancer in patients with a serum prostate-specific antigen less than 20.0 ng/mL. Methods: The prospective study included patients with a prostate-specific antigen level of 2–20 ng/mL, who underwent prostate biopsy. Clinical and pathological data such as age, prostate volume, prostate-specific antigen, procalcitonin, and Gleason score were reviewed. All patients were divided into three groups with total prostate-specific antigen level between 2 and 4 ng/mL, 4.1 and 10 ng/mL, and 10.1 and 20 ng/mL. Results: Of 227 patients who underwent biopsy, prostate cancer was diagnosed in 74 (32.6%) patients and the remaining 153 patients had a benign condition. The difference in mean serum procalcitonin values was significantly higher in the prostate cancer compared with the benign group (0.06 ± 0.03 vs 0.04 ± 0.03 ng/mL; p = 0.0001). Using a threshold of 0.045 ng/mL, procalcitonin was 54.1% sensitive and 80.3% specific (area under curve = 0.683). Serum procalcitonin levels were not able to differentiate between prostate cancer patients with prostate-specific antigen level of 2–4, 4.1–10, and 10.1–20 ng/mL. Conclusion: Based on this prospective study, procalcitonin can be a novel supplementary biomarker to increase the accuracy of prostate cancer screening.
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Gautam, Shailendra K., Parvez Khan, Gopalakrishnan Natarajan, Pranita Atri, Abhijit Aithal, Apar K. Ganti, Surinder K. Batra, Mohd W. Nasser, and Maneesh Jain. "Mucins as Potential Biomarkers for Early Detection of Cancer." Cancers 15, no. 6 (March 7, 2023): 1640. http://dx.doi.org/10.3390/cancers15061640.
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Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients’ sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection.
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Dariane, Charles, Sylvie Clairefond, Benjamin Péant, Laudine Communal, Zhe Thian, Véronique Ouellet, Dominique Trudel, et al. "High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality." Cancers 14, no. 7 (March 23, 2022): 1623. http://dx.doi.org/10.3390/cancers14071623.
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Background: New predictive biomarkers are needed to accurately predict metastasis-free survival (MFS) and cancer-specific survival (CSS) in localized prostate cancer (PC). Keratin-7 (KRT7) overexpression has been associated with poor prognosis in several cancers and is described as a novel prostate progenitor marker in the mouse prostate. Methods: KRT7 expression was evaluated in prostatic cell lines and in human tissue by immunohistochemistry (IHC, on advanced PC, n = 91) and immunofluorescence (IF, on localized PC, n = 285). The KRT7 mean fluorescence intensity (MFI) was quantified in different compartments by digital analysis and correlated to clinical endpoints in the localized PC cohort. Results: KRT7 is expressed in prostatic cell lines and found in the basal and supra-basal compartment from healthy prostatic glands and benign peri-tumoral glands from localized PC. The KRT7 staining is lost in luminal cells from localized tumors and found as an aberrant sporadic staining (2.2%) in advanced PC. In the localized PC cohort, high KRT7 MFI above the 80th percentile in the basal compartment was significantly and independently correlated with MFS and CSS, and with hypertrophic basal cell phenotype. Conclusion: High KRT7 expression in benign glands is an independent biomarker of MFS and CSS, and its expression is lost in tumoral cells. These results require further validation on larger cohorts.
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Meehan, James, Mark Gray, Carlos Martínez-Pérez, Charlene Kay, Duncan McLaren, and Arran K. Turnbull. "Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine." Journal of Personalized Medicine 11, no. 7 (July 15, 2021): 664. http://dx.doi.org/10.3390/jpm11070664.
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Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to stratify patients whose tumours are unlikely to progress from those that are aggressive and require treatment intensification. Although PC-specific biomarker research has previously focused on disease diagnosis, there is an unmet clinical need for novel prognostic, predictive and treatment response biomarkers that can be used to provide a precision medicine approach to PC management. In particular, the identification of biomarkers at the time of screening/diagnosis that can provide an indication of disease aggressiveness is perhaps the greatest current unmet clinical need in PC management. Largely through advances in genomic and proteomic techniques, exciting pre-clinical and clinical research is continuing to identify potential tissue, blood and urine-based PC-specific biomarkers that may in the future supplement or replace current standard practices. In this review, we describe how PC-specific biomarker research is progressing, including the evolution of PSA-based tests and those novel assays that have gained clinical approval. We also describe alternative diagnostic biomarkers to PSA, in addition to biomarkers that can predict PC aggressiveness and biomarkers that can predict response to certain therapies. We believe that novel biomarker research has the potential to make significant improvements to the clinical management of this disease in the near future.
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Shah, Palak, Pushpinder Bawa, Lanbo Xiao, Yelena Kleyman, Josh Vo, Saravana M. Dhanasekaran, Jason Brown, et al. "Abstract 3383: Circular RNAs as non-invasive diagnostic biomarkers for prostate cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3383. http://dx.doi.org/10.1158/1538-7445.am2022-3383.
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Abstract Prostate cancer is one of the most common cancers in men. The disease is largely indolent in nature and treatment of low-risk prostate cancer is not always necessary. However, a fraction of the patients will progress to aggressive disease which accounts for most of the cancer related mortality. Detection methods accurately differentiating between high- and low-risk patients for lethal prostate cancer is a critical need and currently, prostate biopsies and subsequent histopathology and molecular profiling are the most definitive way to differentiate between these two patient populations. But biopsies are invasive procedures associated with significant morbidity. Hence, there exists a critical need to develop non-invasive and highly sensitive diagnostic biomarkers to avoid unnecessary biopsies. Here, we propose to develop a novel biomarker panel which constitutes of a class of RNA molecules called circular RNA (circRNA) to be detected in liquid biopsies. Circular RNAs are covalently closed RNA structures, which are resistant to degradation by exoribonucleases because of the absence of free termini in their nucleotide chain. Due to their increased stability compared to their linear counterparts, circRNAs are ideal candidates for biomarkers, especially in non-invasive liquid biopsies. Using MiOncoCirc, a circRNA compendium from >2,000 primary and metastatic cancer tissues representing 40 cancer types, we first identified 9 circRNAs that are specifically expressed in prostate adenocarcinoma (PRAD) compared to all other cancer types. Next, we examined if these candidates are differentially expressed between PRAD and normal prostate tissues. Based on higher levels of expression which were statistically significant in the PRAD compared to normal prostate tissues, we promoted 4 circRNAs to our biomarker panel. In addition, our panel also includes 2 circRNAs that we predicted to arise from PRAD specific lncRNAs. To study the expression of the novel 6-circRNA biomarker expression in high-risk prostate cancer patients we developed a capture-based RNA sequencing assay. For the initial round we used this assay to test our pilot post-DRE patient urine sample EDRN cohort and detected expression of the prostate cancer-specific circRNAs in a subset of these post-DRE urine samples. We are in the process of expanding our test cohort which will also contain additional clinical annotations such as Gleason score. Post cohort assembly we intend to run our 6-circRNA capture assay on these samples to determine whether the expression levels of candidate circRNAs are correlated with disease stage and other clinical parameters. Our results will facilitate the rapid development of a diagnostic test using non-invasive urine samples for the early detection of high-risk prostate cancer. Citation Format: Palak Shah, Pushpinder Bawa, Lanbo Xiao, Yelena Kleyman, Josh Vo, Saravana M. Dhanasekaran, Jason Brown, Nicolette Loeding, Alexander Koons, Javed Siddiqui, Xuhong Cao, Arul M. Chinnaiyan. Circular RNAs as non-invasive diagnostic biomarkers for prostate 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 3383.
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McGrath, Sophie E., Agnieszka Michael, Richard Morgan, and Hardev Pandha. "EN2: a novel prostate cancer biomarker." Biomarkers in Medicine 7, no. 6 (December 2013): 893–901. http://dx.doi.org/10.2217/bmm.13.115.
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Larkin, Samantha ET, Bashar Zeidan, Matthew G. Taylor, Bridget Bickers, Jamal Al-Ruwaili, Claire Aukim-Hastie, and Paul A. Townsend. "Proteomics in prostate cancer biomarker discovery." Expert Review of Proteomics 7, no. 1 (February 2010): 93–102. http://dx.doi.org/10.1586/epr.09.89.
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Doll, Andreas, Jeremy Clark, and Colleen Nelson. "Biomarker and Translational Prostate Cancer Research." BioMed Research International 2015 (2015): 1. http://dx.doi.org/10.1155/2015/309851.
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Samaržija, Ivana, Koraljka Gall Trošelj, and Paško Konjevoda. "Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning." Cancers 15, no. 4 (February 18, 2023): 1309. http://dx.doi.org/10.3390/cancers15041309.
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Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes SERINC3 (phosphatidylserine and sphingolipids generation) and CSAD (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers.
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Ljubić, Sven, Antonio Sermek, Angela Prgomet Sečan, Marin Prpić, Blanka Jakšić, Jure Murgić, Ana Fröbe, Đurđica Ugarković, and Isidoro Feliciello. "Alpha Satellite RNA Levels Are Upregulated in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer." Genes 13, no. 2 (February 20, 2022): 383. http://dx.doi.org/10.3390/genes13020383.
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The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such as blood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker.
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Bernardino, Rui Miguel Marques, Ricardo Leão, Rui Henrique, Luis Campos Pinheiro, Prashant Kumar, Prashanth Suravajhala, Hans Christian Beck, Ana Sofia Carvalho, and Rune Matthiesen. "Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies." International Journal of Molecular Sciences 22, no. 24 (December 19, 2021): 13605. http://dx.doi.org/10.3390/ijms222413605.
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Molecular diagnostics based on discovery research holds the promise of improving screening methods for prostate cancer (PCa). Furthermore, the congregated information prompts the question whether the urinary extracellular vesicles (uEV) proteome has been thoroughly explored, especially at the proteome level. In fact, most extracellular vesicles (EV) based biomarker studies have mainly targeted plasma or serum. Therefore, in this study, we aim to inquire about possible strategies for urinary biomarker discovery particularly focused on the proteome of urine EVs. Proteomics data deposited in the PRIDE archive were reanalyzed to target identifications of potential PCa markers. Network analysis of the markers proposed by different prostate cancer studies revealed moderate overlap. The recent throughput improvements in mass spectrometry together with the network analysis performed in this study, suggest that a larger standardized cohort may provide potential biomarkers that are able to fully characterize the heterogeneity of PCa. According to our analysis PCa studies based on urinary EV proteome presents higher protein coverage compared to plasma, plasma EV, and voided urine proteome. This together with a direct interaction of the prostate gland and urethra makes uEVs an attractive option for protein biomarker studies. In addition, urinary proteome based PCa studies must also evaluate samples from bladder and renal cancers to assess specificity for PCa.
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Kałuża, Anna, Justyna Szczykutowicz, and Mirosława Ferens-Sieczkowska. "Glycosylation: Rising Potential for Prostate Cancer Evaluation." Cancers 13, no. 15 (July 24, 2021): 3726. http://dx.doi.org/10.3390/cancers13153726.
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Prostate cancer is the second most commonly diagnosed cancer among men. Alterations in protein glycosylation are confirmed to be a reliable hallmark of cancer. Prostate-specific antigen is the biomarker that is used most frequently for prostate cancer detection, although its lack of sensitivity and specificity results in many unnecessary biopsies. A wide range of glycosylation alterations in prostate cancer cells, including increased sialylation and fucosylation, can modify protein function and play a crucial role in many important biological processes in cancer, including cell signalling, adhesion, migration, and cellular metabolism. In this review, we summarize studies evaluating the prostate cancer associated glycosylation related alterations in sialylation, mainly α2,3-sialylation, core fucosylation, branched N-glycans, LacdiNAc group and presence of truncated O-glycans (sTn, sT antigen). Finally, we discuss the great potential to make use of glycans as diagnostic and prognostic biomarkers for prostate cancer.
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Woollam, Mark, Amanda P. Siegel, Adam Munshi, Shengzhi Liu, Sunil Tholpady, Thomas Gardner, Bai-Yan Li, Hiroki Yokota, and Mangilal Agarwal. "Canine-Inspired Chemometric Analysis of Volatile Organic Compounds in Urine Headspace to Distinguish Prostate Cancer in Mice and Men." Cancers 15, no. 4 (February 20, 2023): 1352. http://dx.doi.org/10.3390/cancers15041352.
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Canines can identify prostate cancer with high accuracy by smelling volatile organic compounds (VOCs) in urine. Previous studies have identified VOC biomarkers for prostate cancer utilizing solid phase microextraction (SPME) gas chromatography–mass spectrometry (GC-MS) but have not assessed the ability of VOCs to distinguish aggressive cancers. Additionally, previous investigations have utilized murine models to identify biomarkers but have not determined if the results are translatable to humans. To address these challenges, urine was collected from mice with prostate cancer and men undergoing prostate cancer biopsy and VOCs were analyzed by SPME GC-MS. Prior to analysis, SPME fibers/arrows were compared, and the fibers had enhanced sensitivity toward VOCs with a low molecular weight. The analysis of mouse urine demonstrated that VOCs could distinguish tumor-bearing mice with 100% accuracy. Linear discriminant analysis of six VOCs in human urine distinguished prostate cancer with sensitivity = 75% and specificity = 69%. Another panel of seven VOCs could classify aggressive cancer with sensitivity = 78% and specificity = 85%. These results show that VOCs have moderate accuracy in detecting prostate cancer and a superior ability to stratify aggressive tumors. Furthermore, the overlap in the structure of VOCs identified in humans and mice shows the merit of murine models for identifying biomarker candidates.
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Brawley, Otis W., Ian M. Thompson, and Henrik Grönberg. "Evolving Recommendations on Prostate Cancer Screening." American Society of Clinical Oncology Educational Book, no. 36 (May 2016): e80-e87. http://dx.doi.org/10.1200/edbk_157413.
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Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient.