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Novel Biomarkers for Prostate Cancer Detection and Prognosis

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Cell & Molecular Biology of Prostate Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1095))

Abstract

Prostate cancer (PCa) remains as one of the most controversial issues in health care because of the dilemmas related to screening using Prostate Specific Antigen (PSA). A high number of false positive biopsies and an elevated rate of overdiagnosis are the main problems associated with PSA. New PCa biomarkers have been recently proposed to increase the predictive value of PSA. The published results showed that PCA3 score, Prostate Health Index and 4Kscore can reduce the number of unnecessary biopsies, outperforming better than PSA and the percentage of free PSA. Furthermore, 4Kscore provides with high accuracy an individual risk for high-grade PCa. High values of PHI are also associated with tumor aggressiveness. In contrast, the relationship of PCA3 score with aggressiveness remains controversial, with studies showing opposite conclusions. Finally, the development of molecular biology has opened the study of genes, among them TMPRSS2:ERG fusion gene and miRNAs, in PCa detection and prognosis.

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References

  1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403

    Article  CAS  PubMed  Google Scholar 

  2. Bell KJ, Del Mar C, Wright G, Dickinson J, Glasziou P (2015) Prevalence of incidental prostate cancer: a systematic review of autopsy studies. Int J Cancer 137:1749–1757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Howlader N, Noone AM, Krapcho M, et al, eds. (2015) SEER cancer statistics review, 1975–2012, based on November 2014 SEER data submission. National Cancer Institute, Bethesda;. Available at: https://seer.cancer.gov/archive/csr/1975_2012/results_merged/sect_23_prostate.pdf. Accessed 4 July 2017

    Google Scholar 

  4. Fleshner K, Carlsson SV, Roobol MJ (2017) The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nat Rev Urol 14:26–37

    Article  CAS  PubMed  Google Scholar 

  5. Epstein JI, Walsh PC, Carmichael M, Brendler CB (1994) Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 271:368–374

    Article  CAS  PubMed  Google Scholar 

  6. D’Amico AV, Whittington R, Malkowicz SB et al (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969–974

    Article  PubMed  Google Scholar 

  7. Carter HB, Partin AW, Walsh PC, Trock BJ, Veltri RW, Nelson WG et al (2012) Gleason score 6 adenocarcinoma: should it be labeled as cancer? J Clin Oncol 30:4294–4296

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kulac I, Haffner MC, Yegnasubramanian S, Epstein JI, De Marzo AM (2015) Should Gleason 6 be labeled as cancer? Curr Opin Urol 25:238–245

    Article  PubMed  PubMed Central  Google Scholar 

  9. Eggener SE, Badani K, Barocas DA, Barrisford GW, Cheng JS, Chin AI et al (2015) Gleason 6 prostate Cancer: translating biology into population health. J Urol 194:626–634

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cancer Genome Atlas Research Network (2015) The molecular taxonomy of primary prostate Cancer. Cell 163:1011–1025

    Article  CAS  Google Scholar 

  11. Rubin MA, Girelli G, Demichelis F (2016) Genomic correlates to the newly proposed grading prognostic groups for prostate Cancer. Eur Urol 69:557–560

    Article  PubMed  Google Scholar 

  12. Tosoian JJ, Carter HB, Lepor A, Loeb S (2016) Active surveillance for prostate cancer: current evidence and contemporary state of practice. Nat Rev Urol 13:205–215

    Article  PubMed  PubMed Central  Google Scholar 

  13. Palisaar JR, Noldus J, Löppenberg B, von Bodman C, Sommerer F, Eggert T (2012, Sep) Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. BJU Int 110(6 Pt B):E172–E181

    Article  PubMed  Google Scholar 

  14. Lee R, Localio AR, Armstrong K, Malkowicz SB, Schwartz JS (2006) A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology 67:762–768

    Article  PubMed  Google Scholar 

  15. Mikolajczyk SD, Millar LS, Wang TJ et al (2000) A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue. Cancer Res 60:756–759

    CAS  PubMed  Google Scholar 

  16. Mikolajczyk SD, Grauer LS, Millar LS et al (1997) A precursor form of PSA (pPSA) is a component of the free PSA in prostate cancer serum. Urology 50:710–714

    Article  CAS  PubMed  Google Scholar 

  17. Mikolajczyk SD, Rittenhouse HG (2003) Pro PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer. Keio J Med 52:86–91

    Article  PubMed  Google Scholar 

  18. Sokoll LJ, Chan DW, Mikolajczyk SD, Rittenhouse HG, Evans CL, Linton HJ et al (2003) Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: preliminary analysis. Urology 61:274–276

    Article  PubMed  Google Scholar 

  19. Khan MA, Partin AW, Rittenhouse HG, Mikolajczyk SD, Sokoll LJ, Chan DW et al (2003) Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml. J Urol 170:723–726

    Article  CAS  PubMed  Google Scholar 

  20. Stephan C, Meyer HA, Kwiatkowski M, Recker F, Cammann H, Loening SA et al (2006) A (−5, −7) proPSA based artificial neural network to detect prostate cancer. Eur Urol 50:1014–1020

    Article  PubMed  Google Scholar 

  21. Filella X, Alcover J, Molina R, Luque P, Corral JM, Augé JM et al (2007) Usefulness of proprostate-specific antigen in the diagnosis of prostate cancer. Anticancer Res 27:607–610

    CAS  PubMed  Google Scholar 

  22. Semjonow A, Kopke T, Eltze E, Pepping-Schefers B, Burgel H, Darte C (2010) Pre-analytical in-vitro stability of [−2]proPSA in blood and serum. Clin Biochem 43:926–928

    Article  CAS  PubMed  Google Scholar 

  23. Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bangma CH et al (2011) 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. J Urol 185:1650–1655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stephan C, Vincendeau S, Houlgatte A, Cammann H, Jung K, Semjonow A (2013) Multicenter evaluation of [−2]proprostate-specific antigen and the prostate health index for detecting prostate cancer. Clin Chem 59:306–314

    Article  CAS  PubMed  Google Scholar 

  25. Lazzeri M, Haese A, de la Taille A, Palou J, McNicholas T, Lughezzani G et al (2013) 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. Eur Urol 63:986–994

    Article  CAS  PubMed  Google Scholar 

  26. Filella X, Foj L, Augé JM, Molina R, Alcover J (2014) Clinical utility of %p2PSA and prostate health index in the detection of prostate cancer. Clin Chem Lab Med 52:1347–1355

    Article  CAS  PubMed  Google Scholar 

  27. Loeb S, Sanda MG, Broyles DL, Shin SS, Bangma CH, Wei JT et al (2015) The prostate health index selectively identifies clinically significant prostate cancer. J Urol 193:1163–1169

    Article  PubMed  Google Scholar 

  28. Filella X, Giménez N (2012) Evaluation of [−2]proPSA and prostate health index (phi) for the detection of prostate cancer: a systematic review and meta-analysis. Clin Chem Lab Med 15:1–11

    Article  CAS  Google Scholar 

  29. Wang W, Wang M, Wang L, Adams TS, Tian Y, Xu J (2014) Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis. Sci Rep 4:5012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bruzzese D, Mazzarella C, Ferro M, Perdonà S, Chiodini P, Perruolo G et al (2014) Prostate health index vs. percent free prostate-specific antigen for prostate cancer detection in men with “gray” prostate-specific antigen levels at first biopsy: systematic review and meta-analysis. Transl Res 164:444–451

    Article  PubMed  Google Scholar 

  31. Cantiello F, Russo GI, Ferro M, Cicione A, Cimino S, Favilla V et al (2015) Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy. Urol Oncol 33(163):e15–e23

    Google Scholar 

  32. Heidegger I, Klocker H, Pichler R, Pircher A, Prokop W, Steiner E et al (2017 Mar 21) ProPSA and the prostate health index as predictive markers for aggressiveness in low-risk prostate cancer-results from an international multicenter study. Prostate Cancer Prostatic Dis 20:271–275. https://doi.org/10.1038/pcan.2017.3

    Article  CAS  PubMed  Google Scholar 

  33. De la Calle C, Patil D, Wei JT, Scherr DS, Sokoll L, Chan DW et al (2015) Multicenter evaluation of the prostate health index to detect aggressive prostate cancer in biopsy naïve men. J Urol 194:65–72

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tosoian JJ, Loeb S, Feng Z, Isharwal S, Landis P, Elliot DJ et al (2012) Association of [−2]proPSA with biopsy reclassification during active surveillance for prostate cancer. J Urol 188:1131–1136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vickers AJ, Cronin AM, Aus G, Pihl CG, Becker C, Pettersson K et al (2008) 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 BMC Med 6:19

    Article  PubMed  CAS  Google Scholar 

  36. Vickers A, Cronin A, Roobol M, Savage C, Peltola M, Pettersson K et al (2010) Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication. J Clin Oncol 28:2493–2498

    Article  PubMed  PubMed Central  Google Scholar 

  37. Vickers AJ, Cronin AM, Roobol MJ, Savage CJ, Peltola M, Pettersson K et al (2010) A four-kallikrein panel predicts prostate cancer in men with recent screening: data from the European randomized study of screening for prostate Cancer, Rotterdam. Clin Cancer Res 16:3232–3239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Vickers AJ, Cronin AM, Aus G, Pihl CG, Becker C, Pettersson K et al (2010) Impact of recent screening on predicting the outcome of prostate cancer biopsy in men with elevated prostate specific antigen: data from the European randomized study of prostate Cancer screening in Gothenburg, Sweden. Cancer 116:2612–2620

    PubMed  Google Scholar 

  39. Vickers AJ, Gupta A, Savage CJ, Pettersson K, Dahlin A, Bjartell A et al (2011) A panel of kallikrein marker predicts prostate cancer in a large, population-based cohort followed for 15 years without screening. Cancer Epidemiol Biomark Prev 20:255–261

    Article  CAS  Google Scholar 

  40. Parekh DJ, Punnen S, Sjoberg DD, Asroff SW, Bailen JL, Cochran JS et al (2015) A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol 68:464–470

    Article  PubMed  Google Scholar 

  41. Kim EH, Andriole GL, Crawford ED, Sjoberg DD, Assel M, Vickers AJ et al (2017) Detection of high grade prostate cancer among PLCO participants using a prespecified 4-Kallikrein marker panel. J Urol 197:1041–1047

    Article  PubMed  Google Scholar 

  42. Vickers A, Vertosick EA, Sjoberg DD, Roobol MJ, Hamdy F, Neal D et al (2017) Properties of the 4-Kallikrein panel outside the diagnostic gray zone: meta-analysis of patients with positive digital rectal examination or prostate specific antigen 10 ng/ml and above. J Urol 197(3 Pt 1):607–613

    Article  PubMed  Google Scholar 

  43. Lin DW, Newcomb LF, Brown MD, Sjoberg DD, Dong Y, Brooks JD et al (2016 Nov 23) Evaluating the Four Kallikrein Panel of the 4Kscore for prediction of high-grade prostate cancer in men in the Canary Prostate Active Surveillance Study. Eur Urol pii:S0302–2838(16):30850–30858

    Google Scholar 

  44. Stattin P, Vickers AJ, Sjoberg DD, Johansson R, Granfors T, Johansson M et al (2015) 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 68:207–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lughezzani G, Lazzeri M, Larcher A, Lista G, Scattoni V, Cestari A et al (2012) Development and internal validation of a prostate health index based nomogram for predicting prostate cancer at extended biopsy. J Urol 188:1144–1150

    Article  PubMed  Google Scholar 

  46. Lughezzani G, Lazzeri M, Haese A, McNicholas T, de la Taille A, Buffi NM et al (2014) Multicenter european external validation of a prostate health index-based nomogram for predicting prostate cancer at extended biopsy. Eur Urol 66:906–912

    Article  CAS  PubMed  Google Scholar 

  47. Filella X, Foj L, Alcover J (2014) Aug é JM, Molina R, Jiménez W. The influence of prostate volume in prostate health index performance in patients with total PSA lower than 10 μ g/L. Clin Chim Acta 436:303–307

    Article  CAS  PubMed  Google Scholar 

  48. Roobol M, Vedder MM, Nieboer D, Houlgatte A, Vincendeau S, Lazzeri M et al (2015) Comparison of two prostate Cancer risk calculators that include the prostate health index. European Urology Focus 1:185–190

    Article  PubMed  Google Scholar 

  49. Loeb S, Shin SS, Broyles DL, Wei JT, Sanda M, Klee G et al (2017) Prostate health index improves multivariable risk prediction of aggressive prostate cancer. BJU Int 120:61–68

    Article  CAS  PubMed  Google Scholar 

  50. Leyten GH, Hessels D, Smit FP, Jannink SA, de Jong H, Melchers WJ et al (2015) Identification of a candidate gene panel for the early diagnosis of prostate Cancer. Clin Cancer Res 21:3061–3070

    Article  CAS  PubMed  Google Scholar 

  51. Hessels D, de Jong H, Jannink SA, Carter M, Krispin M, Van Criekinge W et al (2017) Analytical validation of an mRNA-based urine test to predict the presence of high-grade prostate cancer. Translational Medicine Communications 2:5. https://doi.org/10.1186/s41231-017-0014-8

    Article  Google Scholar 

  52. Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA et al (1999) DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 59:5975–5979

    CAS  PubMed  Google Scholar 

  53. Lemos AE, Ferreira LB, Batoreu NM, de Freitas PP, Bonamino MH, Gimba ER (2016) PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells. Tumour Biol 37:11339–11348

    Article  CAS  PubMed  Google Scholar 

  54. Filella X, Foj L, Milà M, Augé JM, Molina R, Jiménez W (2013) PCA3 in the detection and management of early prostate cancer. Tumour Biol 34:1337–1347

    Article  CAS  PubMed  Google Scholar 

  55. Ruiz-Aragón J, Márquez-Peláez S (2010) Assessment of the PCA3 test for prostate cancer diagnosis: a systematic review and metaanalysis. Actas Urol Esp 34:346–355

    Article  PubMed  Google Scholar 

  56. De la Taille A, Irani J, Graefen M, Chun F, de Reijke T, Kil P et al (2011) Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol 185:2119–2125

    Article  PubMed  Google Scholar 

  57. Crawford ED, Rove KO, Trabulsi EJ, Qian J, Drewnowska KP, Kaminetsky JC et al (2012) Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1962 cases. J Urol 188:1726–1731

    Article  PubMed  Google Scholar 

  58. Capoluongo E, Zambon CF, Basso D, Boccia S, Rocchetti S, Leoncini E et al (2014) PCA3 score of 20 could improve prostate cancer detection: results obtained on 734 Italian individuals. Clin Chim Acta 429:46–50

    Article  CAS  PubMed  Google Scholar 

  59. Chevli KK, Duff M, Walter P, Yu C, Capuder B, Elshafei A et al (2014) Urinary PCA3 as a predictor for prostate cancer in a cohort of 3073 men undergoing initial prostate biopsy. J Urol 191:1743–1748

    Article  CAS  PubMed  Google Scholar 

  60. Foj L, Milà M, Mengual L, Luque P, Alcaraz A, Jiménez W et al (2014) Real-time PCR PCA3 assay is a useful test measured in urine to improve prostate cancer detection. Clin Chim Acta 435:53–58

    Article  CAS  PubMed  Google Scholar 

  61. Bradley LA, Palomaki GE, Gutman S, Samson D, Aronson N (2013) Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer. J Urol 190:389–398

    Article  CAS  PubMed  Google Scholar 

  62. Roobol MJ, Schröder FH, van Leeuwen P, Wolters T, van den Bergh RC, van Leenders GJ et al (2010) Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test. Eur Urol 58:475–481

    Article  CAS  PubMed  Google Scholar 

  63. Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF et al (2008) Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol 54:1081–1088

    Article  PubMed  Google Scholar 

  64. Schröder FH, Venderbos LD, van den Bergh RC, Hessels D, van Leenders GJ, van Leeuwen PJ et al (2014) Prostate cancer antigen 3: diagnostic outcomes in men presenting with urinary prostate cancer antigen 3 scores ≥ 100. Urology 83:613–616

    Article  PubMed  Google Scholar 

  65. Auprich M, Chun FK, Ward JF, Pummer K, Babaian R, Augustin H et al (2011) Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging. Eur Urol 59:96–105

    Article  PubMed  Google Scholar 

  66. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW et al (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310:644–648

    Article  CAS  PubMed  Google Scholar 

  67. Deplus R, Delliaux C, Marchand N, Flourens A, Vanpouille N, Leroy X et al (2017) TMPRSS2-ERG fusion promotes prostate cancer metastases in bone. Oncotarget 8:11827–11840

    Article  PubMed  Google Scholar 

  68. Tomlins SA, Laxman B, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS et al (2007) Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 448:595–599

    Article  CAS  PubMed  Google Scholar 

  69. Sanguedolce F, Cormio A, Brunelli M, D'Amuri A, Carrieri G, Bufo P et al (2016) Urine TMPRSS2: ERG fusion transcript as a biomarker for prostate Cancer: literature review. Clin Genitourin Cancer 14:117–121

    Article  PubMed  Google Scholar 

  70. Leyten GH, Hessels D, Jannink SA, Smit FP, de Jong H, Cornel EB et al (2014) Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur Urol 65:534–542

    Article  CAS  PubMed  Google Scholar 

  71. Tomlins SA, Day JR, Lonigro RJ, Hovelson DH, Siddiqui J, Kunju LP et al (2016) Urine TMPRSS2:ERG plus PCA3 for individualized prostate cancer risk assessment. Eur Urol 70:45–53

    Article  CAS  PubMed  Google Scholar 

  72. Sanda MG, Feng Z, Howard DH, Tomlins SA, Sokoll LJ, Chan DW et al (2017 May 18) Association between combined TMPRSS2:ERG and PCA3 RNA urinary testing and detection of aggressive prostate Cancer. JAMA Oncol 3:1085–1093. https://doi.org/10.1001/jamaoncol.2017.0177

    Article  PubMed  PubMed Central  Google Scholar 

  73. Stephan C, Cammann H, Jung K (2015) Re: Scott a. Tomlins, John R. Day, Robert J. Lonigro, et al. urine TMPRSS2:ERG plus PCA3 for individualized prostate Cancer risk assessment. Eur Urol 68:e106–e107

    Article  PubMed  Google Scholar 

  74. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K et al (2010) MicroRNAs and cancer: current state and future perspectives in urologic oncology. Urol Oncol 28:4–13

    Article  CAS  PubMed  Google Scholar 

  76. Brennecke J, Stark A, Russell RB, Cohen SM (2005) Principles of microRNA-target recognition. PLoS Biol 3:e85

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of posttranscriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114

    Article  CAS  PubMed  Google Scholar 

  78. Santarpia L, Nicoloso M, Calin GA (2010) MicroRNAs: a complex regulatory network drives the acquisition of malignant cell phenotype. Endocr Relat Cancer 17:51–75

    Article  CAS  Google Scholar 

  79. Lewis B, Shih I, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of Mammalian MicroRNA Targets. Cell 115:787–798

    Article  CAS  PubMed  Google Scholar 

  80. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ et al (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500

    Article  CAS  PubMed  Google Scholar 

  81. Cava C, Colaprico A, Bertoli G, Graudenzi A, Silva TC, Olsen C et al (2017) SpidermiR: an R/Bioconductor package for integrative analysis with miRNA data. Int J Mol Sci 18(2):27. https://doi.org/10.3390/ijms18020274

    Article  CAS  Google Scholar 

  82. Griffiths-Jones S (2006) miRBase: the microRNA sequence database. Methods Mol Biol Clifton NJ 342:129–138

    CAS  Google Scholar 

  83. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610

    Article  CAS  PubMed  Google Scholar 

  84. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  CAS  PubMed  Google Scholar 

  85. Decatur WA, Fournier MJ (2002) rRNA modifications and ribosome function. Trends Biochem Sci 27:344–351

    Article  CAS  PubMed  Google Scholar 

  86. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105:10513–10518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Mihelich BL, Maranville JC, Nolley R, Peehl DM, Nonn L (2015) Elevated serum microRNA levels associate with absence of high-grade prostate cancer in a retrospective cohort. PLoS One 10:e0124245

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Chen ZH, Zhang GL, Li HR, Luo JD, Li ZX, Chen GM et al (2012) A panel of five circulating microRNAs as potential biomarkers for prostate cancer. Prostate 72:1443–1452

    Article  CAS  PubMed  Google Scholar 

  89. Cheng HH, Mitchell PS, Kroh EM, Dowell AE, Chery L, Siddiqui J et al (2013) Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One 8:e69239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sharova E, Grassi A, Marcer A, Ruggero K, Pinto F, Bassi P et al (2016) A circulating miRNA assay as a first-line test for prostate cancer screening. Br J Cancer 114:1362–1366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Al-Qatati A, Akrong C, Stevic I, Pantel K, Awe J, Saranchuk J et al (2017) Plasma microRNA signature is associated with risk stratification in prostate cancer patients. Int J Cancer 141:1231–1239

    Article  CAS  PubMed  Google Scholar 

  92. Salido-Guadarrama AI, Morales-Montor JG, Rangel-Escareño C, Langley E, Peralta-Zaragoza O, Cruz Colin JL et al (2016) Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone. Mol Med Rep 13:4549–4560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Filella X, Foj L (2017) miRNAs as novel biomarkers in the management of prostate cancer. Clin Chem Lab Med 55:715–736

    Article  CAS  PubMed  Google Scholar 

  94. Selth LA, Townley S, Gillis JL, Ochnik AM, Murti K, Macfarlane RJ et al (2012) Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease. Int J Cancer 131:652–661

    Article  CAS  PubMed  Google Scholar 

  95. Brase JC, Johannes M, Schlomm T, Falth M, Haese A, Steuber T et al (2011) Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128:608–616

    Article  CAS  PubMed  Google Scholar 

  96. Nguyen HC, Xie W, Yang M, Hsieh CL, Drouin S, Lee GS et al (2013) Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer. Prostate 73:346–354

    Article  CAS  PubMed  Google Scholar 

  97. Bryant RJ, Pawlowski T, Catto JW, Marsden G, Vessella RL, Rhees B et al (2012) Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer 106:768–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Fredsøe J, Rasmussen AKI, Thomsen AR, Mouritzen P, Høyer S, Borre M et al (2017 Mar 9) Diagnostic and prognostic microRNA biomarkers for prostate cancer in cell-free urine. Eur Urol Focus. https://doi.org/10.1016/j.euf.2017.02.018

  99. Metcalf GA, Shibakawa A, Patel H, Sita-Lumsden A, Zivi A, Rama N et al (2016) Amplification-free detection of circulating microRNA biomarkers from body fluids based on fluorogenic oligonucleotide-templated reaction between engineered peptide nucleic acid probes: ppplication to prostate cancer diagnosis. Anal Chem 88:8091–8098

    Article  CAS  PubMed  Google Scholar 

  100. Huang X, Yuan T, Tschannen M, Sun Z, Jacob H, Du M et al (2013) Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics 14:319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Théry C, Boussac M, Véron P, Ricciardi-Castagnoli P, Raposo G, Garin J et al (2001) Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 166:7309–7318

    Article  PubMed  Google Scholar 

  103. Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581

    Article  CAS  PubMed  Google Scholar 

  104. Keller S, Sanderson MP, Stoeck A, Altevogt P (2006) Exosomes: from biogenesis and secretion to biological function. Immunol Lett 107:102–108

    Article  CAS  PubMed  Google Scholar 

  105. Cheng L, Sun X, Scicluna BJ, Coleman BM, Hill AF (2014) Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA in human urine. Kidney Int 86:433–444

    Article  CAS  PubMed  Google Scholar 

  106. Cheng L, Sharples RA, Scicluna BJ, Hill AF (2014 Mar) Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles 26:3. https://doi.org/10.3402/jev.v3.23743

    Article  CAS  Google Scholar 

  107. Mall C, Rocke DM, Durbin-Johnson B, Weiss RH (2013) Stability of miRNA in human urine supports its biomarker potential. Biomark Med 7:623–631

    Article  CAS  PubMed  Google Scholar 

  108. Hessvik NP, Sandvigm K, Llorente A (2013) Exosomal miRNAs as biomarkers for prostate Cancer. Front Genet 4:36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM et al (2014) Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci U S A 111:14888–14893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108:5003–5008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Gallo A, Tandon M, Alevizos I, Illei GG (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One 7:e30679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Li Z, Ma YY, Wang J, Zeng XF, Li R, Kang W et al (2015) Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Onco Targets Ther 9:139–148

    PubMed  PubMed Central  Google Scholar 

  114. Huang X, Yuan T, Liang M, Du M, Xia S, Dittmar R et al (2015) Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol 67:33–41

    Article  CAS  PubMed  Google Scholar 

  115. Foj L, Ferrer F, Serra M, Arévalo A, Gavagnach M, Giménez N et al (2017) Exosomal and non-Exosomal urinary miRNAs in prostate Cancer detection and prognosis. Prostate 77:573–583

    Article  CAS  PubMed  Google Scholar 

  116. Samsonov R, Shtam T, Burdakov V, Glotov A, Tsyrlina E, Berstein L et al (2016) Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: application for prostate cancer diagnostic. Prostate 76:68–79

    Article  CAS  PubMed  Google Scholar 

  117. Alhasan AH, Kim DY, Daniel WL, Watson E, Meeks JJ, Thaxton CS et al (2012) Scanometric microRNA array profiling of prostate cancer markers using spherical nucleic acid-gold nanoparticle conjugates. Anal Chem 84:4153–4160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Alhasan AH, Scott AW, Wu JJ, Feng G, Meeks JJ, Thaxton CS et al (2016) Circulating microRNA signature for the diagnosis of very high-risk prostate cancer. Proc Natl Acad Sci U S A 113:10655–10660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Auprich M, Bjartell A, Chun FK, de la Taille A, Freedland SJ, Haese A et al (2011) Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur Urol 60:1045–1054

    Article  CAS  PubMed  Google Scholar 

  120. Russo GI, Regis F, Castelli T, Favilla V, Privitera S, Giardina R et al (2017) A systematic review and meta-analysis of the diagnostic accuracy of prostate health index and 4-kallikrein panel score in predicting overall and high-grade prostate cancer. Clin Genitourin Cancer 15:429–439

    Article  PubMed  Google Scholar 

  121. Nordström T, Vickers A, Assel M, Lilja H, Grönberg H, Eklund M (2015) Comparison between the four-kallikrein panel and prostate health index for predicting prostate Cancer. Eur Urol 68:139–146

    Article  PubMed  CAS  Google Scholar 

  122. Scattoni V, Lazzeri M, Lughezzani G, de Luca S, Passera R, Bollito E et al (2013) Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy. J Urol 190:496–501

    Article  PubMed  Google Scholar 

  123. Stephan C, Jung K, Semjonow A, Schulze-Forster K, Cammann H, Hu X et al (2013) Comparative assessment of urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion with the serum [−2]proprostate-specific antigen-based prostate health index for detection of prostate cancer. Clin Chem 59:280–288

    Article  CAS  PubMed  Google Scholar 

  124. Vedder MM, de Bekker-Grob EW, Lilja HG, Vickers AJ, van Leenders GJ, Steyerberg EW et al (2014) The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallicrein panel to the ERSPC risk calculator for prostate Cancer in prescreened men. Eur Urol 66:1109–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Prostate Cancer Early Detection (2017) National Cancer Comprehensive Network Clinical Practice Guidelines in Oncology. Version I. 2017. Available online: https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf (Accessed on 18 August 2017)

  126. Mottet N, Bellmunt J, Briers E, Bolla M, Cornford P, de Santis M, et al. (n.d.) EAU Guideliness prostate cancer. Available online: http://uroweb.org/guideline/prostate-cancer/ (Accessed on 18 August 2017)

  127. Vickers AJ, Eastham JA, Scardino PT, Lilja H (2016) The memorial Sloan Kettering Cancer center recommendations for prostate Cancer screening. Urology 91:12–18

    Article  PubMed  Google Scholar 

  128. Watson MJ, George AK, Maruf M, Frye TP, Muthigi A, Kongnyuy M et al (2016) Risk stratification of prostate cancer: integrating multiparametric MRI, nomograms and biomarkers. Future Oncol 12:2417–2430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Both authors contributed equally to this manuscript

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  1. Department of Biochemistry and Molecular Genetics (CDB), Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain

    Xavier Filella & Laura Foj

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  1. Xavier Filella
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    Heide Schatten

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Filella, X., Foj, L. (2018). Novel Biomarkers for Prostate Cancer Detection and Prognosis. In: Schatten, H. (eds) Cell & Molecular Biology of Prostate Cancer. Advances in Experimental Medicine and Biology, vol 1095. Springer, Cham. https://doi.org/10.1007/978-3-319-95693-0_2

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