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Cellular Oncology

, Volume 39, Issue 2, pp 97–106 | Cite as

PSA and beyond: alternative prostate cancer biomarkers

  • Sharanjot SainiEmail author
Review

Abstract

Background

The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions.

Methods

A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected.

Conclusions

With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine.

Keywords

Prostate cancer Biomarkers Prognostic Predictive Diagnostic 

Notes

Compliance with ethical standards

The manuscript complies with ethical standards.

Funding

The author is supported by the National Cancer Institute at the National Institutes of Health (Grant Number RO1CA177984).

Conflict of interest

The author declares that there are no conflicts of interest.

References

  1. 1.
    R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2015. CA Cancer J. Clin. 65, 5–29 (2015)CrossRefPubMedGoogle Scholar
  2. 2.
    M.K. Fong, R. Hare, A. Jarkowski, A new era for castrate resistant prostate cancer: a treatment review and update. J. Oncol. Pharm. Pract. 18, 343–354 (2012)CrossRefPubMedGoogle Scholar
  3. 3.
    D.N. Rodrigues, L.M. Butler, D.L. Estelles, J.S. de Bono, Molecular pathology and prostate cancer therapeutics: from biology to bedside. J. Pathol. 232, 178–184 (2013)Google Scholar
  4. 4.
    R.D. Loberg, C.J. Logothetis, E.T. Keller, K.J. Pienta, Pathogenesis and treatment of prostate cancer bone metastases: targeting the lethal phenotype. J. Clin. Oncol. 23, 8232–8241 (2005)CrossRefPubMedGoogle Scholar
  5. 5.
    J. Romero Otero, B. Garcia Gomez, F. Campos Juanatey, K.A. Touijer, Prostate cancer biomarkers: an update. Urol. Oncol. 32, 252–260 (2014)CrossRefPubMedGoogle Scholar
  6. 6.
    H. Lilja, Testing new PSA subforms to enhance the accuracy of predicting cancer risk and disease outcome in prostate cancer. Clin. Chem. 54, 1248–1249 (2008)CrossRefPubMedGoogle Scholar
  7. 7.
    H. Lilja, D. Ulmert, A.J. Vickers, Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat. Rev. Cancer 8, 268–278 (2008)CrossRefPubMedGoogle Scholar
  8. 8.
    K.C. Cary, M.R. Cooperberg, Biomarkers in prostate cancer surveillance and screening: past, present, and future. Ther. Adv. Urol. 5, 318–329 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    J.I. Epstein, An update of the Gleason grading system. J. Urol. 183, 433–440 (2010)CrossRefPubMedGoogle Scholar
  10. 10.
    G.T. Mellinger, D. Gleason, J. Bailar 3rd, The histology and prognosis of prostatic cancer. J. Urol. 97, 331–337 (1967)PubMedGoogle Scholar
  11. 11.
    M.M. Shen, C. Abate-Shen, Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 24, 1967–2000 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    J.A. Squire, P.C. Park, M. Yoshimoto, J. Alami, J.L. Williams, A. Evans et al., Prostate cancer as a model system for genetic diversity in tumors. Adv. Cancer Res. 112, 183–216 (2011)CrossRefPubMedGoogle Scholar
  13. 13.
    J.R. Schoenborn, P. Nelson, M. Fang, Genomic profiling defines subtypes of prostate cancer with the potential for therapeutic stratification. Clin. Cancer Res. 19, 4058–4066 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    S.E. Ilyin, S.M. Belkowski, C.R. Plata-Salaman, Biomarker discovery and validation: technologies and integrative approaches. Trends Biotechnol. 22, 411–416 (2004)CrossRefPubMedGoogle Scholar
  15. 15.
    J.R. Prensner, M.A. Rubin, J.T. Wei, A.M. Chinnaiyan, Beyond PSA: the next generation of prostate cancer biomarkers. Sci. Transl. Med. 4, 127rv123 (2012)Google Scholar
  16. 16.
    C.L. Sawyers, The cancer biomarker problem. Nature 452, 548–552 (2008)CrossRefPubMedGoogle Scholar
  17. 17.
    F.C. Lowe, S.J. Trauzzi, Prostatic acid phosphatase in 1993. Its limited clinical utility. Urol. Clin. North Am. 20, 589–595 (1993)PubMedGoogle Scholar
  18. 18.
    C.J. Ercole, P.H. Lange, M. Mathisen, R.K. Chiou, P.K. Reddy, R.L. Vessella, Prostatic specific antigen and prostatic acid phosphatase in the monitoring and staging of patients with prostatic cancer. J. Urol. 138, 1181–1184 (1987)PubMedGoogle Scholar
  19. 19.
    D.A. Sartori, D.W. Chan, Biomarkers in prostate cancer: what’s new? Curr. Opin. Oncol. 26, 259–264 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    G.J. Kelloff, P. Choyke, D.S. Coffey, Challenges in clinical prostate cancer: role of imaging. AJR Am. J. Roentgenol. 192, 1455–1470 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Y. Mazaheri, A. Shukla-Dave, A. Muellner, H. Hricak, MRI of the prostate: clinical relevance and emerging applications. J. Magn. Reson. Imaging 33, 258–274 (2011)CrossRefPubMedGoogle Scholar
  22. 22.
    K. Bensalah, F. Montorsi, S.F. Shariat, Challenges of cancer biomarker profiling. Eur. Urol. 52, 1601–1609 (2007)CrossRefPubMedGoogle Scholar
  23. 23.
    J. Hernandez, I.M. Thompson, Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker. Cancer 101, 894–904 (2004)CrossRefPubMedGoogle Scholar
  24. 24.
    I.M. Thompson, D.K. Pauler, P.J. Goodman, C.M. Tangen, M.S. Lucia, H.L. Parnes et al., Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N. Engl. J. Med. 350, 2239–2246 (2004)CrossRefPubMedGoogle Scholar
  25. 25.
    W.J. Catalona, D.S. Smith, D.K. Ornstein, Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA 277, 1452–1455 (1997)CrossRefPubMedGoogle Scholar
  26. 26.
    L.C. Walter, D. Bertenthal, K. Lindquist, B.R. Konety, PSA screening among elderly men with limited life expectancies. JAMA 296, 2336–2342 (2006)CrossRefPubMedGoogle Scholar
  27. 27.
    D.D. Brooks, A. Wolf, R.A. Smith, C. Dash, I. Guessous, Prostate cancer screening 2010: updated recommendations from the American Cancer Society. J. Natl. Med. Assoc. 102, 423–429 (2010)CrossRefPubMedGoogle Scholar
  28. 28.
    A.M. Wolf, R.C. Wender, R.B. Etzioni, I.M. Thompson, A.V. D’Amico, R.J. Volk et al., American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J. Clin. 60, 70–98 (2010)CrossRefPubMedGoogle Scholar
  29. 29.
    A.V. D’Amico, M.H. Chen, K.A. Roehl, W.J. Catalona, Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N. Engl. J. Med. 351, 125–135 (2004)CrossRefPubMedGoogle Scholar
  30. 30.
    R. Etzioni, A. Tsodikov, A. Mariotto, A. Szabo, S. Falcon, J. Wegelin et al., Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control 19, 175–181 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    A. Christensson, T. Bjork, O. Nilsson, U. Dahlen, M.T. Matikainen, A.T. Cockett et al., Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J. Urol. 150, 100–105 (1993)PubMedGoogle Scholar
  32. 32.
    W.J. Catalona, A.W. Partin, K.M. Slawin, M.K. Brawer, R.C. Flanigan, A. Patel 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 279, 1542–1547 (1998)CrossRefPubMedGoogle Scholar
  33. 33.
    M.A. Khan, L.J. Sokoll, D.W. Chan, L.A. Mangold, P. Mohr, S.D. Mikolajczyk et al., Clinical utility of proPSA and “benign” PSA when percent free PSA is less than 15 %. Urology 64, 1160–1164 (2004)CrossRefPubMedGoogle Scholar
  34. 34.
    S. Hori, J.S. Blanchet, J. McLoughlin, 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. 112, 717–728 (2013)CrossRefPubMedGoogle Scholar
  35. 35.
    S.D. Mikolajczyk, K.M. Marker, L.S. Millar, A. Kumar, M.S. Saedi, J.K. Payne et al., A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res. 61, 6958–6963 (2001)PubMedGoogle Scholar
  36. 36.
    T.Y. Chan, S.D. Mikolajczyk, K. Lecksell, M.J. Shue, H.G. Rittenhouse, A.W. Partin et al., Immunohistochemical staining of prostate cancer with monoclonal antibodies to the precursor of prostate-specific antigen. Urology 62, 177–181 (2003)CrossRefPubMedGoogle Scholar
  37. 37.
    I. Heidegger, H. Klocker, E. Steiner, V. Skradski, M. Ladurner, R. Pichler et al., [-2]proPSA is an early marker for prostate cancer aggressiveness. Prostate Cancer Prostatic Dis. 17, 70–74 (2014)CrossRefPubMedGoogle Scholar
  38. 38.
    M. Lazzeri, A. Abrate, G. Lughezzani, G.M. Gadda, M. Freschi, F. Mistretta 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 83, 606–612 (2014)CrossRefPubMedGoogle Scholar
  39. 39.
    M. Lazzeri, A. Haese, A. Abrate, A. de la Taille, J.P. Redorta, T. McNicholas 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. 112, 313–321 (2013)CrossRefPubMedGoogle Scholar
  40. 40.
    G. Guazzoni, L. Nava, M. Lazzeri, V. Scattoni, G. Lughezzani, C. Maccagnano 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. 60, 214–222 (2011)CrossRefPubMedGoogle Scholar
  41. 41.
    A. Houlgatte, S. Vincendeau, F. Desfemmes, J. Ramirez, N. Benoist, K. Bensalah et al., Use of [-2] pro PSA and phi index for early detection of prostate cancer: a prospective of 452 patients. Prog. Urol. 22, 279–283 (2012)CrossRefPubMedGoogle Scholar
  42. 42.
    L.J. Sokoll, M.G. Sanda, Z. Feng, J. Kagan, I.A. Mizrahi, D.L. Broyles 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. 19, 1193–1200 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    M.J. Bussemakers, A. van Bokhoven, G.W. Verhaegh, F.P. Smit, H.F. Karthaus, J.A. Schalken et al., DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res. 59, 5975–5979 (1999)PubMedGoogle Scholar
  44. 44.
    J.B. de Kok, G.W. Verhaegh, R.W. Roelofs, D. Hessels, L.A. Kiemeney, T.W. Aalders et al., DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 62, 2695–2698 (2002)PubMedGoogle Scholar
  45. 45.
    M. Auprich, A. Bjartell, F.K. Chun, A. de la Taille, S.J. Freedland, A. Haese et al., Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur. Urol. 60, 1045–1054 (2011)CrossRefPubMedGoogle Scholar
  46. 46.
    E.D. Crawford, K.O. Rove, E.J. Trabulsi, J. Qian, K.P. Drewnowska, J.C. Kaminetsky 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. 188, 1726–1731 (2012)CrossRefPubMedGoogle Scholar
  47. 47.
    V. Vlaeminck-Guillem, A. Ruffion, J. Andre, M. Devonec, P. Paparel, Urinary prostate cancer 3 test: toward the age of reason? Urology 75, 447–453 (2010)CrossRefPubMedGoogle Scholar
  48. 48.
    I.L. Deras, S.M. Aubin, A. Blase, J.R. Day, S. Koo, A.W. Partin et al., PCA3: a molecular urine assay for predicting prostate biopsy outcome. J. Urol. 179, 1587–1592 (2008)CrossRefPubMedGoogle Scholar
  49. 49.
    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. (2015). doi: 10.1016/j.eururo.2015.04.039
  50. 50.
    G.H. Leyten, D. Hessels, S.A. Jannink, F.P. Smit, H. de Jong, E.B. Cornel et al., Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur. Urol. 65, 534–542 (2014)CrossRefPubMedGoogle Scholar
  51. 51.
    E. Schiffer, Biomarkers for prostate cancer. World J. Urol. 25, 557–562 (2007)CrossRefPubMedGoogle Scholar
  52. 52.
    S.S. Salami, F. Schmidt, B. Laxman, M.M. Regan, D.S. Rickman, D. Scherr et al., Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. Urol. Oncol. 31, 566–571 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    D. Knezevic, A.D. Goddard, N. Natraj, D.B. Cherbavaz, K.M. Clark-Langone, J. Snable et al., Analytical validation of the Oncotype DX prostate cancer assay - a clinical RT-PCR assay optimized for prostate needle biopsies. BMC Genomics 14, 690 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    P. Blume-Jensen, D.M. Berman, D.L. Rimm, M. Shipitsin, M. Putzi, T.P. Nifong et al., Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clin. Cancer Res. 21, 2591–2600 (2015)CrossRefPubMedGoogle Scholar
  55. 55.
    J.N. Cornu, G. Cancel-Tassin, C. Egrot, C. Gaffory, F. Haab, O. Cussenot, Urine TMPRSS2:ERG fusion transcript integrated with PCA3 score, genotyping, and biological features are correlated to the results of prostatic biopsies in men at risk of prostate cancer. Prostate 73, 242–249 (2013)CrossRefPubMedGoogle Scholar
  56. 56.
    M.R. Cooperberg, J.P. Simko, J.E. Cowan, J.E. Reid, A. Djalilvand, S. Bhatnagar et al., Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J. Clin. Oncol. 31, 1428–1434 (2013)CrossRefPubMedGoogle Scholar
  57. 57.
    J. Cuzick, D.M. Berney, G. Fisher, D. Mesher, H. Moller, J.E. Reid et al., Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br. J. Cancer 106, 1095–1099 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    S.J. Freedland, L. Gerber, J. Reid, W. Welbourn, E. Tikishvili, J. Park 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. 86, 848–853 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    R.L. Parr, J. Mills, A. Harbottle, J.M. Creed, G. Crewdson, B. Reguly et al., Mitochondria, prostate cancer, and biopsy sampling error. Discov. Med. 15, 213–220 (2013)PubMedGoogle Scholar
  60. 60.
    M.L. Verschoor, R. Ungard, A. Harbottle, J.P. Jakupciak, R.L. Parr, G. Singh, Mitochondria and cancer: past, present, and future. Biomed Res Int 2013, 612369 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    K. Robinson, J. Creed, B. Reguly, C. Powell, R. Wittock, D. Klein et al., Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay. Prostate Cancer Prostatic Dis. 13, 126–131 (2010)CrossRefPubMedGoogle Scholar
  62. 62.
    S. Carlsson, A. Maschino, F. Schroder, C. Bangma, E.W. Steyerberg, T. 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. Eur. Urol. 64, 693–699 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    J.D. Voigt, S.M. Zappala, E.D. Vaughan, A.J. Wein, The Kallikrein panel for prostate cancer screening: its economic impact. Prostate 74, 250–259 (2014)CrossRefPubMedGoogle Scholar
  64. 64.
    A. Sreekumar, L.M. Poisson, T.M. Rajendiran, A.P. Khan, Q. Cao, J. Yu et al., Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457, 910–914 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    K. Badani, D.J. Thompson, C. Buerki, E. Davicioni, J. Garrison, M. Ghadessi 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 4, 600–609 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    E.D. Crawford, K. Ventii, N.D. Shore, New biomarkers in prostate cancer. Oncology (Williston Park) 28, 135–142 (2014)Google Scholar
  67. 67.
    M.A. Rubin, M. Zhou, S.M. Dhanasekaran, S. Varambally, T.R. Barrette, M.G. Sanda et al., alpha-Methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA 287, 1662–1670 (2002)CrossRefPubMedGoogle Scholar
  68. 68.
    M.A. Rubin, T.A. Bismar, O. Andren, L. Mucci, R. Kim, R. Shen et al., Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death. Cancer Epidemiol. Biomarkers Prev. 14, 1424–1432 (2005)CrossRefPubMedGoogle Scholar
  69. 69.
    Z. Jiang, G.R. Fanger, B.A. Woda, B.F. Banner, P. Algate, K. Dresser et al., Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases. Hum. Pathol. 34, 792–796 (2003)CrossRefPubMedGoogle Scholar
  70. 70.
    P. Cairns, K. Okami, S. Halachmi, N. Halachmi, M. Esteller, J.G. Herman et al., Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res. 57, 4997–5000 (1997)PubMedGoogle Scholar
  71. 71.
    B.S. Carver, C. Chapinski, J. Wongvipat, H. Hieronymus, Y. Chen, S. Chandarlapaty et al., Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19, 575–586 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Bostrom PJ, Bjartell AS, Catto JW, Eggener SE, Lilja H, Loeb S et al., Genomic predictors of outcome in prostate cancer. Eur. Urol. (2015). doi: 10.1016/j.eururo.2015.04.008
  73. 73.
    K. Sircar, M. Yoshimoto, F.A. Monzon, I.H. Koumakpayi, R.L. Katz, A. Khanna et al., PTEN genomic deletion is associated with p-Akt and AR signalling in poorer outcome, hormone refractory prostate cancer. J. Pathol. 218, 505–513 (2009)CrossRefPubMedGoogle Scholar
  74. 74.
    A. Krohn, T. Diedler, L. Burkhardt, P.S. Mayer, C. De Silva, M. Meyer-Kornblum et al., Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. Am. J. Pathol. 181, 401–412 (2012)CrossRefPubMedGoogle Scholar
  75. 75.
    K.A. Leinonen, O.R. Saramaki, B. Furusato, T. Kimura, H. Takahashi, S. Egawa et al., Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. Cancer Epidemiol. Biomarkers Prev. 22, 2333–2344 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    M. Yoshimoto, A.M. Joshua, I.W. Cunha, R.A. Coudry, F.P. Fonseca, O. Ludkovski et al., Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod. Pathol. 21, 1451–1460 (2008)CrossRefPubMedGoogle Scholar
  77. 77.
    L.H. Broersen, G.W. van Pelt, R.A. Tollenaar, W.E. Mesker, Clinical application of circulating tumor cells in breast cancer. Cell. Oncol. 37, 9–15 (2014)Google Scholar
  78. 78.
    D.C. Danila, G. Heller, G.A. Gignac, R. Gonzalez-Espinoza, A. Anand, E. Tanaka et al., Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin. Cancer Res. 13, 7053–7058 (2007)CrossRefPubMedGoogle Scholar
  79. 79.
    M.J. Kim, N.Y. Choi, E.K. Lee, M.S. Kang, Identification of novel markers that outperform EpCAM in quantifying circulating tumor cells. Cell. Oncol. 37, 235–243 (2014)Google Scholar
  80. 80.
    G. Attard, J.F. Swennenhuis, D. Olmos, A.H. Reid, E. Vickers, R. A’Hern et al., Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 69, 2912–2918 (2009)CrossRefPubMedGoogle Scholar
  81. 81.
    J.S. de Bono, H.I. Scher, R.B. Montgomery, C. Parker, M.C. Miller, H. Tissing et al., Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin. Cancer Res. 14, 6302–6309 (2008)CrossRefPubMedGoogle Scholar
  82. 82.
    D.P. Bartel, MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    A. Gordanpour, R.K. Nam, L. Sugar, A. Seth, MicroRNAs in prostate cancer: from biomarkers to molecularly-based therapeutics. Prostate Cancer Prostatic Dis. 15, 314–319 (2012)CrossRefPubMedGoogle Scholar
  84. 84.
    D.R. Hurst, M.D. Edmonds, D.R. Welch, Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res. 69, 7495–7498 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    S. Saini, S. Majid, R. Dahiya, Diet, microRNAs and prostate cancer. Pharm. Res. 27, 1014–1026 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    S. Saini, S. Majid, S. Yamamura, L. Tabatabai, S.O. Suh, V. Shahryari et al., Regulatory role of mir-203 in prostate cancer progression and metastasis. Clin. Cancer Res. 17, 5287–5298 (2011)CrossRefPubMedGoogle Scholar
  87. 87.
    I. Giusti, V. Dolo, Extracellular vesicles in prostate cancer: new future clinical strategies? Biomed Res Int 2014, 561571 (2014)PubMedPubMedCentralGoogle Scholar
  88. 88.
    Y. Xi, G. Nakajima, E. Gavin, C.G. Morris, K. Kudo, K. Hayashi et al., Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 13, 1668–1674 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    J.A. Weber, D.H. Baxter, S. Zhang, D.Y. Huang, K.H. Huang, M.J. Lee et al., The microRNA spectrum in 12 body fluids. Clin. Chem. 56, 1733–1741 (2010)CrossRefPubMedGoogle Scholar
  90. 90.
    S. Dijkstra, P.F. Mulders, J.A. Schalken, Clinical use of novel urine and blood based prostate cancer biomarkers: a review. Clin. Biochem. 47, 889–896 (2014)CrossRefPubMedGoogle Scholar
  91. 91.
    J. Szczyrba, E. Loprich, S. Wach, V. Jung, G. Unteregger, S. Barth et al., The microRNA profile of prostate carcinoma obtained by deep sequencing. Mol. Cancer Res. 8, 529–538 (2010)CrossRefPubMedGoogle Scholar
  92. 92.
    A. Schaefer, M. Jung, H.J. Mollenkopf, I. Wagner, C. Stephan, F. Jentzmik et al., Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int. J. Cancer 126, 1166–1176 (2010)PubMedGoogle Scholar
  93. 93.
    P.S. Mitchell, R.K. Parkin, E.M. Kroh, B.R. Fritz, S.K. Wyman, E.L. Pogosova-Agadjanyan et al., Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. U. S. A. 105, 10513–10518 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    F. Moltzahn, A.B. Olshen, L. Baehner, A. Peek, L. Fong, H. Stoppler et al., Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res. 71, 550–560 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    R.J. Bryant, T. Pawlowski, J.W. Catto, G. Marsden, R.L. Vessella, B. Rhees et al., Changes in circulating microRNA levels associated with prostate cancer. Br. J. Cancer 106, 768–774 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    S. Mathivanan, H. Ji, R.J. Simpson, Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73, 1907–1920 (2010)CrossRefPubMedGoogle Scholar
  97. 97.
    D. Duijvesz, T. Luider, C.H. Bangma, G. Jenster, Exosomes as biomarker treasure chests for prostate cancer. Eur. Urol. 59, 823–831 (2011)CrossRefPubMedGoogle Scholar
  98. 98.
    G. Tavoosidana, G. Ronquist, S. Darmanis, J. Yan, L. Carlsson, D. Wu et al., Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc. Natl. Acad. Sci. U. S. A. 108, 8809–8814 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    J. Nilsson, J. Skog, A. Nordstrand, V. Baranov, L. Mincheva-Nilsson, X.O. Breakefield et al., Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br. J. Cancer 100, 1603–1607 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    S. Khan, J.M. Jutzy, M.M. Valenzuela, D. Turay, J.R. Aspe, A. Ashok et al., Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS ONE 7, e46737 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    A. Cannistraci, A.L. Di Pace, R. De Maria, D. Bonci, MicroRNA as new tools for prostate cancer risk assessment and therapeutic intervention: results from clinical data set and patients’ samples. Biomed Res Int 2014, 146170 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    M.A. Cortez, C. Bueso-Ramos, J. Ferdin, G. Lopez-Berestein, A.K. Sood, G.A. Calin, MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat. Rev. Clin. Oncol. 8, 467–477 (2011)CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society for Cellular Oncology 2016

Authors and Affiliations

  1. 1.Department of Urology, Urology Research (112J)Veterans Affairs Medical CenterSan FranciscoUSA
  2. 2.University of California San FranciscoSan FranciscoUSA

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