Along with significant advances in prostate cancer biology research, we also observe the rapid development of modern diagnostic tests. New biomarkers are derived to detect disease while it is organ-confined to stratify the risk and to aid clinical decision-making. Majority of these tools have already been validated clinically, but only a few have received premarket clearance and administration approval. Superiority of novel tests is visible not only in improved detection accuracy but predominantly in the assessment of tumour aggressiveness and selection of patients eligible for conservative management. Two factors limiting the clinical implementation of validated biomarker candidates are costs and local availability. For these reasons, currently, their true clinical role starts after routine screening with prostate-specific antigen test. With this review of prostate cancer biomarkers, we attempted to draw general conclusions on clinical perspectives of these novel tools.

Keywords:
Biomarkers, Molecular tests, Prostate cancer, Screening, Panel tests
1.
Arnold M, Karim-Kos HE, Coebergh JW, Byrnes G, Antilla A, Ferlay J, et al: Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European cancer observatory. Eur J Cancer Oxf Engl 1990. 2015;51:1164-1187.
2.
Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, et al: Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet Lond Engl 2014;384:2027-2035.
3.
Andriole GL, Crawford ED, Grubb RL, Buys SS, Chia D, Church TR, et al: Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012;104:125-132.
4.
Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, et al: Prevalence of prostate cancer among men with a prostate-specific antigen level < or=4.0 ng per milliliter. N Engl J Med 2004;350:2239-2246.
5.
Sangster-Guity N, Tu-Sekine B, Raben DM, Denmeade SR, Williams SA: Mutational analysis of prostate-specific antigen defines the intrinsic proteolytic activity of the proPSA zymogen. Prostate 2016;76:1203-1217.
6.
Lee YJ, Park JE, Jeon BR, Lee SM, Kim SY, Lee YK: Is prostate-specific antigen effective for population screening of prostate cancer? A systematic review. Ann Lab Med 2013;33:233-241.
7.
Bjurlin MA, Mendhiratta N, Wysock JS, Taneja SS: Multiparametric MRI and targeted prostate biopsy: improvements in cancer detection, localization, and risk assessment. Cent Eur J Urol 2016;69:9-18.
8.
Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al: EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2017;71:618-629.
9.
Vickers AJ, Savage C, O'Brien MF, Lilja H: Systematic review of pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer. J Clin Oncol 2009;27:398-403.
10.
Patel HD, Feng Z, Landis P, Trock BJ, Epstein JI, Carter HB: Prostate specific antigen velocity risk count predicts biopsy reclassification for men with very low risk prostate cancer. J Urol 2014;191:629-637.
11.
Loeb S, Metter EJ, Kan D, Roehl KA, Catalona WJ: Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer. BJU Int 2012;109:508-513; discussion 513-514.
12.
Loeb S, Bruinsma SM, Nicholson J, Briganti A, Pickles T, Kakehi Y, et al: Active surveillance for prostate cancer: a systematic review of clinicopathologic variables and biomarkers for risk stratification. Eur Urol 2015;67:619-626.
13.
Christensson A, Björk T, Nilsson O, Dahlén U, Matikainen MT, Cockett AT, et al: Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol 1993;150:100-105.
14.
Catalona WJ, Partin AW, Slawin KM, Brawer MK, Flanigan RC, Patel A, et al: Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. JAMA 1998;279:1542-1547.
15.
Khan MA, Sokoll LJ, Chan DW, Mangold LA, Mohr P, Mikolajczyk SD, et al: Clinical utility of proPSA and ‘benign' PSA when percent free PSA is less than 15%. Urology 2004;64:1160-1164.
16.
Foj L, Filella X, Alcover J, Augé JM, Escudero JM, Molina R: Variability of assay methods for total and free PSA after WHO standardization. Tumour Biol J Int Soc Oncodevelopmental Biol Med 2014;35:1867-1873.
17.
Faria EF, Carvalhal GF, dos Reis RB, Tobias-Machado M, Vieira RAC, Reis LO, et al: Use of low free to total PSA ratio in prostate cancer screening: detection rates, clinical and pathological findings in Brazilian men with serum PSA levels <4.0 ng/mL. BJU Int 2012;110(11 pt B):E653-E657.
18.
Masieri L, Minervini A, Vittori G, Lanciotti M, Lanzi F, Lapini A, et al: The role of free to total PSA ratio in prediction of extracapsular tumor extension and biochemical recurrence after radical prostatectomy in patients with PSA between 4 and 10 ng/ml. Int Urol Nephrol 2012;44:1031-1038.
19.
Sokoll LJ, Sanda MG, Feng Z, Kagan J, Mizrahi IA, Broyles DL, et al: A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [-2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol Biomarkers Prev 2010;19:1193-1200.
20.
Guazzoni G, Nava L, Lazzeri M, Scattoni V, Lughezzani G, Maccagnano C, et al: Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting. Eur Urol 2011;60:214-222.
21.
Heijnsdijk EAM, Denham D, de Koning HJ: The cost-effectiveness of prostate cancer detection with the use of prostate health index. Value Health 2016;19:153-157.
22.
de la Calle C, Patil D, Wei JT, Scherr DS, Sokoll L, Chan DW, et al: Multicenter evaluation of the prostate health index to detect aggressive prostate cancer in biopsy naïve men. J Urol 2015;194:65-72.
23.
Hori S, Blanchet JS, McLoughlin J: From prostate-specific antigen (PSA) to precursor PSA (proPSA) isoforms: a review of the emerging role of proPSAs in the detection and management of early prostate cancer. BJU Int 2013;112:717-728.
24.
Lazzeri M, Abrate A, Lughezzani G, Gadda GM, Freschi M, Mistretta F, et al: Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination. Urology 2014;83:606-612.
25.
Lazzeri M, Haese A, Abrate A, de la Taille A, Redorta JP, McNicholas T, et al: Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project. BJU Int 2013;112:313-321.
26.
De Luca S, Passera R, Fiori C, Bollito E, Cappia S, Mario Scarpa R, et al: Prostate health index and prostate cancer gene 3 score but not percent-free prostate specific antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy. Urol Oncol 2015;33:424.e17-e23.
27.
Lughezzani G, Lazzeri M, Buffi NM, Abrate A, Mistretta FA, Hurle R, et al: Preoperative prostate health index is an independent predictor of early biochemical recurrence after radical prostatectomy: results from a prospective single-center study. Urol Oncol 2015;33:337.e7-e14.
28.
Cantiello F, Russo GI, Ferro M, Cicione A, Cimino S, Favilla V, et al: Prognostic accuracy of prostate health index and urinary prostate cancer antigen 3 in predicting pathologic features after radical prostatectomy. Urol Oncol 2015;33:163.e15-e23.
29.
Fossati N, Buffi NM, Haese A, Stephan C, Larcher A, McNicholas T, et al: Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer: results from a multicentric European prospective study. Eur Urol 2015;68:132-138.
30.
Porpiglia F, Russo F, Manfredi M, Mele F, Fiori C, Bollito E, et al: The roles of multiparametric magnetic resonance imaging, PCA3 and prostate health index-which is the best predictor of prostate cancer after a negative biopsy? J Urol 2014;192:60-66.
31.
Porpiglia F, Cantiello F, De Luca S, Manfredi M, Veltri A, Russo F, et al: In-parallel comparative evaluation between multiparametric magnetic resonance imaging, prostate cancer antigen 3 and the prostate health index in predicting pathologically confirmed significant prostate cancer in men eligible for active surveillance. BJU Int 2016;118:527-534.
32.
Gnanapragasam VJ, Burling K, George A, Stearn S, Warren A, Barrett T, et al: The prostate health index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population. Sci Rep 2016;6:35364.
33.
Carlsson S, Maschino A, Schröder F, Bangma C, Steyerberg EW, van der Kwast T, 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. Eur Urol 2013;64:693-699.
34.
McGrath S, Christidis D, Perera M, Hong SK, Manning T, Vela I, et al: Prostate cancer biomarkers: are we hitting the mark? Prostate Int 2016;4:130-135.
35.
Voigt JD, Zappala SM, Vaughan ED, Wein AJ: The Kallikrein Panel for prostate cancer screening: its economic impact. Prostate 2014;74:250-259.
36.
Vedder MM, de Bekker-Grob EW, Lilja HG, Vickers AJ, van Leenders GJLH, Steyerberg EW, et al: The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC risk calculator for prostate cancer in prescreened men. Eur Urol 2014;66:1109-1115.
37.
Nordström T, Vickers A, Assel M, Lilja H, Grönberg H, Eklund M: Comparison between the four-kallikrein panel and prostate health index for predicting prostate cancer. Eur Urol 2015;68:139-146.
38.
Stattin P, Vickers AJ, Sjoberg DD, Johansson R, Granfors T, Johansson M, 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. Eur Urol 2015;68:207-213.
39.
Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al: DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999;59:5975-5979.
40.
Gezer U, Tiryakioglu D, Bilgin E, Dalay N, Holdenrieder S: Androgen stimulation of PCA3 and miR-141 and their release from prostate cancer cells. Cell J 2015;16:488-493.
41.
Deras IL, Aubin SMJ, Blase A, Day JR, Koo S, Partin AW, et al: PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol 2008;179:1587-1592.
42.
Donovan MJ, Noerholm M, Bentink S, Belzer S, Skog J, O'Neill V, et al: A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate Cancer Prostatic Dis 2015;18:370-375.
43.
Zheng K, Dou Y, He L, Li H, Zhang Z, Chen Y, et al: Improved sensitivity and specificity for prostate cancer diagnosis based on the urine PCA3/PSA ratio acquired by sequence-specific RNA capture. Oncol Rep 2015;34:2439-2444.
44.
Auprich M, Bjartell A, Chun FK-H, de la Taille A, Freedland SJ, Haese A, et al: Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur Urol 2011;60:1045-1054.
45.
Crawford ED, Rove KO, Trabulsi EJ, Qian J, Drewnowska KP, Kaminetsky JC, et al: Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1,962 cases. J Urol 2012;188:1726-1731.
46.
Gittelman MC, Hertzman B, Bailen J, Williams T, Koziol I, Henderson RJ, et al: PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol 2013;190:64-69.
47.
van Poppel H, Haese A, Graefen M, de la Taille A, Irani J, de Reijke T, et al: The relationship between prostate cancer gene 3 (PCA3) and prostate cancer significance. BJU Int 2012;109:360-366.
48.
Malavaud B, Cussenot O, Mottet N, Rozet F, Ruffion A, Smets L, et al: Impact of adoption of a decision algorithm including PCA3 for repeat biopsy on the costs for prostate cancer diagnosis in France. J Med Econ 2013;16:358-363.
49.
Seisen T, Rouprêt M, Brault D, Léon P, Cancel-Tassin G, Compérat E, et al: Accuracy of the prostate health index versus the urinary prostate cancer antigen 3 score to predict overall and significant prostate cancer at initial biopsy. Prostate 2015;75:103-111.
50.
Kaufmann S, Bedke J, Gatidis S, Hennenlotter J, Kramer U, Notohamiprodjo M, et al: Prostate cancer gene 3 (PCA3) is of additional predictive value in patients with PI-RADS grade III (intermediate) lesions in the MR-guided re-biopsy setting for prostate cancer. World J Urol 2016;34:509-515.
51.
De Luca S, Passera R, Cattaneo G, Manfredi M, Mele F, Fiori C, et al: High prostate cancer gene 3 (PCA3) scores are associated with elevated Prostate Imaging Reporting and Data System (PI-RADS) grade and biopsy Gleason score, at magnetic resonance imaging/ultrasonography fusion software-based targeted prostate biopsy after a previous negative standard biopsy. BJU Int 2016;118:723-730.
52.
Cantiello F, Russo GI, Cicione A, Ferro M, Cimino S, Favilla V, et al: PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance. World J Urol 2016;34:485-493.
53.
Hansen J, Auprich M, Ahyai SA, de la Taille A, van Poppel H, Marberger M, et al: Initial prostate biopsy: development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay. Eur Urol 2013;63:201-209.
54.
Rubio-Briones J, Borque A, Esteban LM, Casanova J, Fernandez-Serra A, Rubio L, et al: Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy. BMC Cancer 2015;15:633.
55.
Elshafei A, Chevli KK, Moussa AS, Kara O, Chueh SC, Walter P, et al: PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy. Prostate 2015;75:1951-1957.
56.
Knezevic D, Goddard AD, Natraj N, Cherbavaz DB, Clark-Langone KM, Snable J, et al: Analytical validation of the Oncotype DX prostate cancer assay - a clinical RT-PCR assay optimized for prostate needle biopsies. BMC Genomics 2013;14:690.
57.
Klein EA, Cooperberg MR, Magi-Galluzzi C, Simko JP, Falzarano SM, Maddala T, et al: A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014;66:550-560.
58.
Cullen J, Rosner IL, Brand TC, Zhang N, Tsiatis AC, Moncur J, 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. Eur Urol 2015;68:123-131.
59.
Cuzick J, Swanson GP, Fisher G, Brothman AR, Berney DM, Reid JE, et al: Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol 2011;12:245-255.
60.
Cuzick J, Berney DM, Fisher G, Mesher D, Møller H, Reid JE, et al: Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 2012;106:1095-1099.
61.
Cooperberg MR, Simko JP, Cowan JE, Reid JE, Djalilvand A, Bhatnagar S, et al: Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol 2013;31:1428-1434.
62.
Bishoff JT, Freedland SJ, Gerber L, Tennstedt P, Reid J, Welbourn W, et al: Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. J Urol 2014;192:409-414.
63.
Freedland SJ, Gerber L, Reid J, Welbourn W, Tikishvili E, Park J, et al: Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int J Radiat Oncol Biol Phys 2013;86:848-853.
64.
Cuzick J, Stone S, Fisher G, Yang ZH, North BV, Berney DM, et al: Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br J Cancer 2015;113:382-389.
65.
Ukimura O, Gross ME, de Castro Abreu AL, Azhar RA, Matsugasumi T, Ushijima S, et al: A novel technique using three-dimensionally documented biopsy mapping allows precise re-visiting of prostate cancer foci with serial surveillance of cell cycle progression gene panel. Prostate 2015;75:863-871.
66.
Sommariva S, Tarricone R, Lazzeri M, Ricciardi W, Montorsi F: Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. Eur Urol 2016;69:107-115.
67.
Karnes RJ, Bergstralh EJ, Davicioni E, Ghadessi M, Buerki C, Mitra AP, et al: Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol 2013;190:2047-2053.
68.
Erho N, Crisan A, Vergara IA, Mitra AP, Ghadessi M, Buerki C, et al: Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One 2013;8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691249/.
69.
Badani K, Thompson DJS, Buerki C, Davicioni E, Garrison J, Ghadessi M, et al: Impact of a genomic classifier of metastatic risk on postoperative treatment recommendations for prostate cancer patients: a report from the DECIDE study group. Oncotarget 2013;4:600-609.
70.
Ross AE, Feng FY, Ghadessi M, Erho N, Crisan A, Buerki C, et al: A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy. Prostate Cancer Prostatic Dis 2014;17:64-69.
71.
Den RB, Yousefi K, Trabulsi EJ, Abdollah F, Choeurng V, Feng FY, et al: Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol 2015;33:944-951.
72.
Klein EA, Yousefi K, Haddad Z, Choeurng V, Buerki C, Stephenson AJ, et al: A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. Eur Urol 2015;67:778-786.
73.
Michalopoulos SN, Kella N, Payne R, Yohannes P, Singh A, Hettinger C, et al: Influence of a genomic classifier on post-operative treatment decisions in high-risk prostate cancer patients: results from the PRO-ACT study. Curr Med Res Opin 2014;30:1547-1556.
74.
Freedland SJ, Choeurng V, Howard L, De Hoedt A, du Plessis M, Yousefi K, et al: Utilization of a genomic classifier for prediction of metastasis following salvage radiation therapy after radical prostatectomy. Eur Urol 2016;70:588-596.
75.
Cooperberg MR, Davicioni E, Crisan A, Jenkins RB, Ghadessi M, Karnes RJ: Combined value of validated clinical and genomic risk stratification tools for predicting prostate cancer mortality in a high-risk prostatectomy cohort. Eur Urol 2015;67:326-333.
76.
Den RB, Santiago-Jimenez M, Alter J, Schliekelman M, Wagner JR, Renzulli Ii JF, et al: Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients. Prostate Cancer Prostatic Dis 2016;19:374-379.
77.
Klein EA, Santiago-Jiménez M, Yousefi K, Robbins BA, Schaeffer EM, Trock BJ, et al: Molecular analysis of low grade prostate cancer using a genomic classifier of metastatic potential. J Urol 2017;197:122-128.
78.
Mohler JL, Armstrong AJ, Bahnson RR, DʼAmico AV, Davis BJ, Eastham JA, et al: Prostate cancer, version 1.2016. J Natl Compr Canc Netw 2016;14:19-30.
79.
Stewart GD, Van Neste L, Delvenne P, Delrée P, Delga A, McNeill SA, et al: Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol 2013;189:1110-1116.
80.
Partin AW, Van Neste L, Klein EA, Marks LS, Gee JR, Troyer DA, et al: Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol 2014;192:1081-1087.
81.
Truong M, Yang B, Livermore A, Wagner J, Weeratunga P, Huang W, et al: Using the epigenetic field defect to detect prostate cancer in biopsy negative patients. J Urol 2013;189:2335-2341.
82.
Mehrotra J, Varde S, Wang H, Chiu H, Vargo J, Gray K, et al: Quantitative, spatial resolution of the epigenetic field effect in prostate cancer. Prostate 2008;68:152-160.
83.
Van Neste L, Partin AW, Stewart GD, Epstein JI, Harrison DJ, Van Criekinge W: Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies. Prostate 2016;76:1078-1087.
84.
Zelic R, Fiano V, Zugna D, Grasso C, Delsedime L, Daniele L, et al: Global hypomethylation (LINE-1) and gene-specific hypermethylation (GSTP1) on Initial negative prostate biopsy as markers of prostate cancer on a rebiopsy. Clin Cancer Res 2016;22:984-992.
85.
Paziewska A, Dabrowska M, Goryca K, Antoniewicz A, Dobruch J, Mikula M, et al: DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy. Br J Cancer 2014;111:781-789.
86.
Zhao F, Olkhov-Mitsel E, van der Kwast T, Sykes J, Zdravic D, Venkateswaran V, et al: Urinary DNA methylation biomarkers for noninvasive prediction of aggressive disease in patients with prostate cancer on active surveillance. J Urol 2017;197:335-341.
87.
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644-648.
88.
Thangapazham R, Saenz F, Katta S, Mohamed AA, Tan SH, Petrovics G, et al: Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer. BMC Cancer 2014;14:16.
89.
Tian TV, Tomavo N, Huot L, Flourens A, Bonnelye E, Flajollet S, et al: Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis: involvement of MMP9 and PLXNA2. Oncogene 2014;33:2204-2214.
90.
Cai C, Wang H, Xu Y, Chen S, Balk SP: Reactivation of androgen receptor-regulated TMPRSS2:ERG gene expression in castration-resistant prostate cancer. Cancer Res 2009;69:6027-6032.
91.
Geybels MS, Alumkal JJ, Luedeke M, Rinckleb A, Zhao S, Shui IM, et al: Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors. Clin Epigenetics 2015;7:128.
92.
Bories PN, Younes P, Zerbib M, Denjean L, Popovici T, Cynober L, et al: TMPRSS2-ERG fusion transcripts in matched urine and needle rinse material after biopsy for the detection of prostate cancer. Clin Chem 2013;59:245-251.
93.
Fine SW, Gopalan A, Leversha MA, Al-Ahmadie HA, Tickoo SK, Zhou Q, et al: TMPRSS2-ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features. Mod Pathol 2010;23:1325-1333.
94.
Saramäki OR, Harjula AE, Martikainen PM, Vessella RL, Tammela TLJ, Visakorpi T: TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res 2008;14:3395-1400.
95.
Gopalan A, Leversha MA, Satagopan JM, Zhou Q, Al-Ahmadie HA, Fine SW, et al: TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res 2009;69:1400-1406.
96.
Eguchi FC, Faria EF, Scapulatempo Neto C, Longatto-Filho A, Zanardo-Oliveira C, Taboga SR, et al: The role of TMPRSS2:ERG in molecular stratification of PCa and its association with tumor aggressiveness: a study in Brazilian patients. Sci Rep 2014;4:5640.
97.
Martínez-Piñeiro L, Schalken JA, Cabri P, Maisonobe P, de la Taille A; Triptocare Study Group: Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer. BJU Int 2014;114:608-616.
98.
Font-Tello A, Juanpere N, de Muga S, Lorenzo M, Lorente JA, Fumado L, et al: Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels. Prostate 2015;75:1216-1226.
99.
Yao Y, Wang H, Li B, Tang Y: Evaluation of the TMPRSS2:ERG fusion for the detection of prostate cancer: a systematic review and meta-analysis. Tumour Biol J Int Soc Oncodevelopmental Biol Med 2014;35:2157-2166.
100.
Leyten GHJM, Hessels D, Jannink SA, Smit FP, de Jong H, Cornel EB, et al: Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur Urol 2014;65:534-542.
101.
Sabaliauskaite R, Jarmalaite S, Petroska D, Dasevicius D, Laurinavicius A, Jankevicius F, et al: Combined analysis of TMPRSS2-ERG and TERT for improved prognosis of biochemical recurrence in prostate cancer. Genes Chromosomes Cancer 2012;51:781-791.
102.
Reig Ò, Marín-Aguilera M, Carrera G, Jiménez N, Paré L, García-Recio S, et al: TMPRSS2-ERG in blood and docetaxel resistance in metastatic castration-resistant prostate cancer. Eur Urol 2016;70:709-713.
103.
Robert G, Jannink S, Smit F, Aalders T, Hessels D, Cremers R, et al: Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis. Prostate 2013;73:113-120.
104.
Tomlins SA, Aubin SMJ, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S, et al: Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med 2011;3:94ra72.
105.
Tomlins SA, Day JR, Lonigro RJ, Hovelson DH, Siddiqui J, Kunju LP, et al: Urine TMPRSS2:ERG Plus PCA3 for individualized prostate cancer risk assessment. Eur Urol 2016;70:45-53.
106.
Salami SS, Schmidt F, Laxman B, Regan MM, Rickman DS, Scherr D, et al: Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. Urol Oncol 2013;31:566-571.
107.
Merdan S, Tomlins SA, Barnett CL, Morgan TM, Montie JE, Wei JT, et al: Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy. Cancer 2015;121:4071-4079.
108.
Prensner JR, Iyer MK, Sahu A, Asangani IA, Cao Q, Patel L, et al: The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet 2013;45:1392-1398.
109.
Mehra R, Shi Y, Udager AM, Prensner JR, Sahu A, Iyer MK, et al: A novel RNA in situ hybridization assay for the long noncoding RNA SChLAP1 predicts poor clinical outcome after radical prostatectomy in clinically localized prostate cancer. Neoplasia N Y N 2014;16:1121-1127.
110.
Prensner JR, Zhao S, Erho N, Schipper M, Iyer MK, Dhanasekaran SM, et al: RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncol 2014;15:1469-1480.
111.
Mehra R, Udager AM, Ahearn TU, Cao X, Feng FY, Loda M, et al: Overexpression of the long non-coding RNA SCHLAP1 independently predicts lethal prostate cancer. Eur Urol 2016;70:549-552.
112.
Ma W, Chen X, Ding L, Ma J, Jing W, Lan T, et al: The prognostic value of long noncoding RNAs in prostate cancer: a systematic review and meta-analysis. Oncotarget 2017, Epub ahead of print.
113.
Chua MLK, Lo W, Pintilie M, Murgic J, Lalonde E, Bhandari V, et al: A prostate cancer ‘nimbosus': genomic instability and SChLAP1 dysregulation underpin aggression of intraductal and cribriform subpathologies. Eur Urol 2017, Epub ahead of print.
114.
Nilsson J, Skog J, Nordstrand A, Baranov V, Mincheva-Nilsson L, Breakefield XO, et al: Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 2009;100:1603-1607.
115.
Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008;10:1470-1476.
116.
McKiernan J, Donovan MJ, OʼNeill V, Bentink S, Noerholm M, Belzer S, et al: A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncol 2016;2:882-889.
117.
McDermed JE, Sanders R, Fait S, Klem RE, Sarno MJ, Adams TH, et al: Nucleic acid detection immunoassay for prostate-specific antigen based on immuno-PCR methodology. Clin Chem 2012;58:732-740.
118.
Moul JW, Lilja H, Semmes OJ, Lance RS, Vessella RL, Fleisher M, et al: NADiA® ProsVueTM PSA slope is an independent prognostic marker for identifying men at reduced risk for clinical recurrence of prostate cancer after radical prostatectomy. Urology 2012;80:1319-1325.
119.
Moul JW, Sarno MJ, McDermed JE, Triebell MT, Reynolds MA: NADiA ProsVue prostate-specific antigen slope, CAPRA-S, and prostate cancer - specific survival after radical prostatectomy. Urology 2014;84:1427-1432.
120.
Moul JW, Chen DYT, Trabulsi EJ, Warlick CA, Ruckle HC, Porter JR, et al: Impact of NADiA ProsVue PSA slope on secondary treatment decisions after radical prostatectomy. Prostate Cancer Prostatic Dis 2014;17:280-285.
121.
Reed SD, Stewart SB, Scales CD, Moul JW: A framework to evaluate the cost-effectiveness of the NADiA ProsVue slope to guide adjuvant radiotherapy among men with high-risk characteristics following prostatectomy for prostate cancer. Value Health 2014;17:545-554.
122.
Stroun M, Anker P, Lyautey J, Lederrey C, Maurice PA: Isolation and characterization of DNA from the plasma of cancer patients. Eur J Cancer Clin Oncol 1987;23:707-712.
123.
Beck J, Urnovitz HB, Riggert J, Clerici M, Schütz E: Profile of the circulating DNA in apparently healthy individuals. Clin Chem 2009;55:730-738.
124.
Allen D, Butt A, Cahill D, Wheeler M, Popert R, Swaminathan R: Role of cell-free plasma DNA as a diagnostic marker for prostate cancer. Ann N Y Acad Sci 2004;1022:76-80.
125.
Feng J, Gang F, Li X, Jin T, Houbao H, Yu C, et al: Plasma cell-free DNA and its DNA integrity as biomarker to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate-specific antigen. Int Urol Nephrol 2013;45:1023-1028.
126.
Schütz E, Akbari MR, Beck J, Urnovitz H, Zhang WW, Bornemann-Kolatzki K, et al: Chromosomal instability in cell-free DNA is a serum biomarker for prostate cancer. Clin Chem 2015;61:239-248.
127.
Heitzer E, Ulz P, Belic J, Gutschi S, Quehenberger F, Fischereder K, et al: Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing. Genome Med 2013;5:30.
128.
Leyten GHJM, Hessels D, Smit FP, Jannink SA, de Jong H, Melchers WJG, et al: Identification of a candidate gene panel for the early diagnosis of prostate cancer. Clin Cancer Res 2015;21:3061-3070.
129.
Van Neste L, Hendriks RJ, Dijkstra S, Trooskens G, Cornel EB, Jannink SA, et al: Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Eur Urol 2016;70:740-748.
© 2017 S. Karger AG, Basel
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.