A Rich Array of Prostate Cancer Molecular Biomarkers: Opportunities and Challenges

Prostate cancer is the most prevalent non-skin cancer in men and is the leading cause of cancer-related death. Early detection of prostate cancer is largely determined by a widely used prostate specific antigen (PSA) blood test and biopsy is performed for definitive diagnosis. Prostate cancer is asymptomatic in the early stage of the disease, comprises of diverse clinico-pathologic and progression features, and is characterized by a large subset of the indolent cancer type. Therefore, it is critical to develop an individualized approach for early detection, disease stratification (indolent vs. aggressive), and prediction of treatment response for prostate cancer. There has been remarkable progress in prostate cancer biomarker discovery, largely through advancements in genomic technologies. A rich array of prostate cancer diagnostic and prognostic tests has emerged for serum (4K, phi), urine (Progensa, T2-ERG, ExoDx, SelectMDx), and tumor tissue (ConfirmMDx, Prolaris, Oncoytype DX, Decipher). The development of these assays has created new opportunities for improving prostate cancer diagnosis, prognosis, and treatment decisions. While opening exciting opportunities, these developments also pose unique challenges in terms of selecting and incorporating these assays into the continuum of prostate cancer patient care.

[1]  L. Kiemeney,et al.  DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. , 2002, Cancer research.

[2]  X. Filella,et al.  Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers , 2016, International journal of molecular sciences.

[3]  J. Tchinda,et al.  Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer , 2005, Science.

[4]  S. Srivastava,et al.  Ethnicity and ERG frequency in prostate cancer , 2018, Nature Reviews Urology.

[5]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[6]  S. Srivastava,et al.  Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities , 2018, International journal of molecular sciences.

[7]  Martin E. Gleave,et al.  Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer , 2015, Clinical Cancer Research.

[8]  G. Assmann,et al.  Isolation of prostate-derived single cells and cell clusters from human peripheral blood. , 1996, Cancer research.

[9]  S. Srivastava,et al.  Oncogenic activation of ERG: A predominant mechanism in prostate cancer , 2011, Journal of carcinogenesis.

[10]  Kazutoshi Fujita,et al.  Specific detection of prostate cancer cells in urine by multiplex immunofluorescence cytology. , 2009, Human pathology.

[11]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[12]  David L Rimm,et al.  Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer , 2015, Clinical Cancer Research.

[13]  A. Hartmann,et al.  Expression of GP88 (Progranulin) Protein Is an Independent Prognostic Factor in Prostate Cancer Patients , 2019, Cancers.

[14]  A. Haese*,et al.  Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study. , 2013, European urology.

[15]  E. Fearon,et al.  Cancer progression , 1999, Current Biology.

[16]  Ludmila V. Danilova,et al.  Detection and localization of surgically resectable cancers with a multi-analyte blood test , 2018, Science.

[17]  W. Catalona,et al.  The Prostate Health Index: a new test for the detection of prostate cancer , 2014, Therapeutic advances in urology.

[18]  J. Crowley,et al.  Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. , 2004, The New England journal of medicine.

[19]  David Chia,et al.  Mortality results from a randomized prostate-cancer screening trial. , 2009, The New England journal of medicine.

[20]  Jianbo Li,et al.  Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk. , 2016, Urology.

[21]  K. Bibbins-Domingo,et al.  The US Preventive Services Task Force 2017 Draft Recommendation Statement on Screening for Prostate Cancer: An Invitation to Review and Comment. , 2017, JAMA.

[22]  Y Pawitan,et al.  TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort , 2007, Oncogene.

[23]  P. Febbo,et al.  A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease. , 2018, European urology.

[24]  Andrew J. Vickers,et al.  NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016. , 2016, Journal of the National Comprehensive Cancer Network : JNCCN.

[25]  G. Thalmann,et al.  Metastases in Prostate Cancer. , 2019, Cold Spring Harbor perspectives in medicine.

[26]  Kassandra I. Alcaraz,et al.  Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities , 2016, CA: a cancer journal for clinicians.

[27]  F. Feng,et al.  Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  V. Moyer,et al.  Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement , 2012, Annals of Internal Medicine.

[29]  S. Bentink,et al.  A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result , 2015, Prostate Cancer and Prostatic Disease.

[30]  A. Bilancio,et al.  Non-Genomic Androgen Action Regulates Proliferative/Migratory Signaling in Stromal Cells , 2014, Front. Endocrinol..

[31]  Christopher J Kane,et al.  Prostate Cancer, Version 1.2016. , 2016, Journal of the National Comprehensive Cancer Network : JNCCN.

[32]  R. Vessella,et al.  Evaluation of the Abbott IMx automated immunoassay of prostate-specific antigen. , 1992, Clinical chemistry.

[33]  W. Catalona,et al.  Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. , 1991, The New England journal of medicine.

[34]  Leonard S. Marks,et al.  APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. , 2006, Clinical chemistry.

[35]  P. Carroll,et al.  A Prospective Adaptive Utility Trial to Validate Performance of a Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer in Patients with Prostate-specific Antigen 2-10ng/ml at Initial Biopsy. , 2018, European urology.

[36]  Lu Yu,et al.  PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer. , 2016, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[37]  R. Fort,et al.  vtRNA2-1/nc886 Produces a Small RNA That Contributes to Its Tumor Suppression Action through the microRNA Pathway in Prostate Cancer , 2020, Non-coding RNA.

[38]  D. Chan,et al.  Clinical utility of proPSA and "benign" PSA when percent free PSA is less than 15%. , 2004, Urology.

[39]  Nan Zhang,et al.  A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer. , 2015, European urology.

[40]  Yair Lotan,et al.  Can urinary PCA3 supplement PSA in the early detection of prostate cancer? , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  A. Partin,et al.  Risk score predicts high‐grade prostate cancer in DNA‐methylation positive, histopathologically negative biopsies , 2016, The Prostate.

[42]  R. Vessella,et al.  Detection and characterization of circulating and disseminated prostate cancer cells. , 2007, Frontiers in bioscience : a journal and virtual library.

[43]  B. Trock,et al.  Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens. , 2017, European urology.

[44]  Jeonifer M. Garren,et al.  Clinical Validation of a Serum Protein Panel (FLNA, FLNB and KRT19) for Diagnosis of Prostate Cancer , 2017, Journal of molecular biomarkers & diagnosis.

[45]  Aviv Regev,et al.  Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer , 2014, Nature Biotechnology.

[46]  T. D. de Reijke,et al.  Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer , 2015, Clinical Cancer Research.

[47]  Anirban P. Mitra,et al.  Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy , 2013, PloS one.

[48]  Thomas L. Fillmore,et al.  Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression , 2020, Cancers.

[49]  E. Colás,et al.  PSGR and PCA3 as biomarkers for the detection of prostate cancer in urine , 2010, The Prostate.

[50]  J. Shimazaki,et al.  Progression of prostate cancer to neuroendocrine cell tumor , 2001, International journal of urology : official journal of the Japanese Urological Association.

[51]  Wim Van Criekinge,et al.  Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. , 2013, The Journal of urology.

[52]  E. Colás,et al.  A Three‐Gene panel on urine increases PSA specificity in the detection of prostate cancer , 2011, The Prostate.

[53]  M. Loda,et al.  Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error , 2014, British Journal of Cancer.

[54]  Kenneth J. Pienta,et al.  Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis , 2013, Nature Communications.

[55]  B. Trock,et al.  Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. , 2014, The Journal of urology.

[56]  Jeffrey D. Voigt,et al.  The Kallikrein Panel for prostate cancer screening: Its economic impact , 2014, The Prostate.

[57]  Javed Siddiqui,et al.  Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment. , 2016, European urology.

[58]  W. Ellis,et al.  Early tumor cell dissemination in patients with clinically localized carcinoma of the prostate. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[59]  Tamara S. Adams,et al.  Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis , 2014, Scientific Reports.

[60]  Andrew J Vickers,et al.  A Panel of Kallikrein Marker Predicts Prostate Cancer in a Large, Population-Based Cohort Followed for 15 Years without Screening , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[61]  Andrew J Vickers,et al.  A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden , 2008, BMC medicine.

[62]  John T. Wei,et al.  A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. , 2016, JAMA oncology.

[63]  Nallasivam Palanisamy,et al.  Urine TMPRSS2:ERG Fusion Transcript Stratifies Prostate Cancer Risk in Men with Elevated Serum PSA , 2011, Science Translational Medicine.

[64]  C. Frezza The role of mitochondria in the oncogenic signal transduction. , 2014, The international journal of biochemistry & cell biology.

[65]  C C Schulman,et al.  Optimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1,051 men. , 2000, The Journal of urology.

[66]  O. Nilsson,et al.  Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. , 1991, Clinical chemistry.

[67]  C. Croce,et al.  Detection of hematogenous micrometastasis in patients with prostate cancer. , 1992, Cancer research.

[68]  J. Ardura,et al.  Role of Calcium Signaling in Prostate Cancer Progression: Effects on Cancer Hallmarks and Bone Metastatic Mechanisms , 2020, Cancers.

[69]  J Alfred Witjes,et al.  DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. , 2003, European urology.

[70]  G. Petrovics,et al.  Re: Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and Detection of Aggressive Prostate Cancer. , 2018, European urology.

[71]  P. Scardino,et al.  Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case-Control Study. , 2015, European urology.

[72]  V. Toscano,et al.  Correspondence re: J. B. de Kok et al., DD3, A very sensitive and specific marker to detect prostate tumors. Cancer Res., 62: 2695-2698, 2002. , 2003, Cancer research.

[73]  Dan Mercola,et al.  Plasma-Derived Exosomal Survivin, a Plausible Biomarker for Early Detection of Prostate Cancer , 2012, PloS one.

[74]  V. Srikantan,et al.  Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome , 2005, Oncogene.

[75]  J. Schalken,et al.  Urinary biomarkers for prostate cancer: a review. , 2013, Asian journal of andrology.

[76]  K. Pienta,et al.  Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer , 2008, Clinical Cancer Research.

[77]  L. Amler,et al.  PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients , 2015, British Journal of Cancer.

[78]  S. Srivastava,et al.  Prostate cancer marker panel with single cell sensitivity in urine , 2015, The Prostate.

[79]  W. Isaacs,et al.  AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. , 2014, The New England journal of medicine.

[80]  S. Srivastava,et al.  Prostate cancer: Diagnostic performance of the PCA3 urine test , 2011, Nature Reviews Urology.

[81]  Dante diTommaso,et al.  Quantifying the role of PSA screening in the US prostate cancer mortality decline , 2008, Cancer Causes & Control.

[82]  W. Ellis,et al.  Detection and isolation of prostate cancer cells from peripheral blood and bone marrow. , 2003, Urology.

[83]  F. Saad,et al.  uPM3, a new molecular urine test for the detection of prostate cancer. , 2004, Urology.

[84]  C. Paweletz,et al.  Characterization of intracellular prostate-specific antigen from laser capture microdissected benign and malignant prostatic epithelium. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[85]  F. Mostofi,et al.  Prostate-specific antigen values at the time of prostate cancer diagnosis in African-American men. , 1995, JAMA.

[86]  H. Roca,et al.  Immune mediators in the tumor microenvironment of prostate cancer , 2017, Chinese journal of cancer.

[87]  L. Klotz,et al.  Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay , 2010, Prostate Cancer and Prostatic Diseases.

[88]  W. Isaacs,et al.  DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. , 1999, Cancer research.

[89]  B. Trock,et al.  An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011 , 2013, BJU international.

[90]  Xiaohua Li,et al.  Diagnostic significance of urinary long non-coding PCA3 RNA in prostate cancer , 2017, Oncotarget.

[91]  M. Augustus,et al.  PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[92]  P. Febbo,et al.  A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. , 2014, European urology.

[93]  T. Rebbeck,et al.  Cancer Genomics: Diversity and Disparity Across Ethnicity and Geography. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[94]  J. Moul,et al.  Diagnostic potential of prostate-specific antigen expressing epithelial cells in blood of prostate cancer patients. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[95]  J. Witjes,et al.  Molecular PCA3 diagnostics on prostatic fluid , 2007, The Prostate.

[96]  F. Hamdy,et al.  Changes in circulating microRNA levels associated with prostate cancer , 2012, British Journal of Cancer.

[97]  I. Powell,et al.  Epidemiology, pathology, and genetics of prostate cancer among African Americans compared with other ethnicities. , 2009, Methods in molecular biology.

[98]  P. Carroll,et al.  NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016. , 2016, Journal of the National Comprehensive Cancer Network : JNCCN.

[99]  Guido Jenster,et al.  Exosomes as biomarker treasure chests for prostate cancer. , 2011, European urology.

[100]  T. Rebbeck Prostate Cancer Disparities by Race and Ethnicity: From Nucleotide to Neighborhood. , 2018, Cold Spring Harbor perspectives in medicine.

[101]  P. Carroll,et al.  Prostate cancer early detection version 1 , 2014 .

[102]  Yuzhuo Wang,et al.  Androgen hormone action in prostatic carcinogenesis: stromal androgen receptors mediate prostate cancer progression, malignant transformation and metastasis. , 2012, Carcinogenesis.

[103]  Amy Blase,et al.  PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. , 2007, Urology.

[104]  Ziding Feng,et al.  Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. , 2006, Journal of the National Cancer Institute.

[105]  Geert Trooskens,et al.  Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score. , 2016, European urology.

[106]  J. Schalken,et al.  New targets for therapy in prostate cancer: differential display code 3 (DD3(PCA3)), a highly prostate cancer-specific gene. , 2003, Urology.

[107]  J. Moul,et al.  Quantitative expression profile of PSGR in prostate cancer , 2006, Prostate Cancer and Prostatic Diseases.

[108]  J. Oesterling,et al.  Prostate specific antigen: a decade of discovery--what we have learned and where we are going. , 1999, The Journal of urology.

[109]  X. Breakefield,et al.  Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer , 2009, British Journal of Cancer.

[110]  Martina Tinzl,et al.  DD3PCA3 RNA analysis in urine--a new perspective for detecting prostate cancer. , 2004, European urology.

[111]  P. Pauwels,et al.  Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer , 2017, Clinical and Translational Oncology.

[112]  Anirban P. Mitra,et al.  A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy , 2013, Prostate Cancer and Prostatic Disease.

[113]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[114]  John T. Wei,et al.  Association Between Combined TMPRSS2: ERG and PCA3 RNA Urinary Testing and Detection of Aggressive Prostate Cancer , 2017, JAMA oncology.

[115]  T. H. van der Kwast,et al.  Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam. , 2013, European urology.

[116]  R. Bertolla,et al.  Prostate cancer proteomics: clinically useful protein biomarkers and future perspectives , 2018, Expert review of proteomics.

[117]  John T. Wei,et al.  Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. , 2013, Urologic oncology.

[118]  Erik Holmberg,et al.  Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. , 2010, The Lancet. Oncology.

[119]  L. Kiemeney,et al.  DD3PCA3-based Molecular Urine Analysis for the Diagnosis of Prostate Cancer , 2003 .

[120]  Matti Nykter,et al.  Genomic Alterations in Cell-Free DNA and Enzalutamide Resistance in Castration-Resistant Prostate Cancer. , 2016, JAMA oncology.

[121]  Yair Lotan,et al.  Systematic review of complications of prostate biopsy. , 2013, European urology.

[122]  P. Altevogt,et al.  Body fluid derived exosomes as a novel template for clinical diagnostics , 2011, Journal of Translational Medicine.

[123]  V. Castronovo,et al.  Increased expression of galectin‐1 in carcinoma‐associated stroma predicts poor outcome in prostate carcinoma patients , 2001, The Journal of pathology.

[124]  P. Acher,et al.  Clinical utility and cost modelling of the phi test to triage referrals into image-based diagnostic services for suspected prostate cancer: the PRIM (Phi to RefIne Mri) study , 2020, BMC Medicine.

[125]  A. Jemal,et al.  Cancer statistics, 2019 , 2019, CA: a cancer journal for clinicians.

[126]  G. Murphy,et al.  Purification of a human prostate specific antigen. , 1979, Investigative urology.

[127]  M. Choti,et al.  Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies , 2014, Science Translational Medicine.

[128]  Wei Xiong,et al.  Role of tumor microenvironment in tumorigenesis , 2017, Journal of Cancer.

[129]  M. Brunelli,et al.  Urine TMPRSS2: ERG Fusion Transcript as a Biomarker for Prostate Cancer: Literature Review. , 2016, Clinical genitourinary cancer.

[130]  D. Chan,et al.  Biomarkers in prostate cancer: what's new? , 2014, Current opinion in oncology.

[131]  Sweta Rani,et al.  miR‐34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression , 2014, The Prostate.

[132]  M. Boutros,et al.  Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker * , 2017, Molecular & Cellular Proteomics.

[133]  T. D. de Reijke,et al.  Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. , 2014, European urology.

[134]  P. Troncoso,et al.  PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. , 2008, The Journal of urology.

[135]  Caroline Dive,et al.  Molecular analysis of circulating tumour cells—biology and biomarkers , 2014, Nature Reviews Clinical Oncology.

[136]  K. Pantel,et al.  Cell-free Tumor DNA in Blood Plasma As a Marker for Circulating Tumor Cells in Prostate Cancer , 2009, Clinical Cancer Research.

[137]  S. Srivastava,et al.  Evaluation of the ETS-Related Gene mRNA in Urine for the Detection of Prostate Cancer , 2010, Clinical Cancer Research.

[138]  I. Powell Prostate cancer in the African American: is this a different disease? , 1998, Seminars in urologic oncology.

[139]  R. Nawroth,et al.  Detection of circulating tumor cells in different stages of prostate cancer , 2013, Journal of Cancer Research and Clinical Oncology.

[140]  F. Guimont,et al.  Mitochondria, prostate cancer, and biopsy sampling error. , 2013, Discovery medicine.

[141]  I. Powell The precise role of ethnicity and family history on aggressive prostate cancer: a review analysis. , 2011, Archivos espanoles de urologia.

[142]  John T. Wei,et al.  A multicenter study of [-2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range. , 2011, The Journal of urology.

[143]  S. Srivastava,et al.  PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. , 2008, The Journal of urology.

[144]  U. Landegren,et al.  Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer , 2011, Proceedings of the National Academy of Sciences.

[145]  Anirban P. Mitra,et al.  Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. , 2013, The Journal of urology.