Preview

Research and Practical Medicine Journal

Advanced search

Current biomarkers of prostate cancer

https://doi.org/10.17709/2410-1893-2021-8-4-10

Abstract

Prostate cancer is one of the most common malignancies in men. Early detection of prostate cancer is largely determined by the widely used prostate specific antigen (PSA) blood test. However, as a diagnostic and prognostic test of prostate cancer, PSA has limited specificity, sensitivity and leads to hyper or underdiagnosis, which, in turn, can lead to excessive treatment. There fore, it is very important to develop diagnostic markers that can be used to determine prostate cancer at an early stage of development, assess the possible progression of the disease and prescribe optimal therapy. Significant progress has been made in the discovery of biomarkers for prostate cancer. For example, biomarkers such as %-free PSA, Prostate Health Index (PHI) or 4K score can be used to increase specificity and reduce the number of unnecessary biopsies, while the PCA3 test can be used to reduce the number of repeated biopsies in men with previously negative biopsy. To determine aggressiveness and predict the outcome of the disease, tissue multigenic tests can be used, such as: T2-ERG, ExoDx, SelectMDx and ConfirmMDx, Prolaris, Oncoytype DX, Decipher. The development of such diagnostic tests opens up new opportunities for improving the diagnosis of prostate cancer, prognosis and decision-making on the appointment of therapy. And with the increase in their availability, finally, the possibility of an individual approach to the appointment of treatment for men with prostate cancer appears on the horizon. This review paper presents the data on the most advanced diagnostic biomarkers of prostate cancer.

About the Authors

I. A. Aboian
Clinical and Diagnostic Center "Zdorovie"
Russian Federation

Igor A. Aboian – Dr. Sci. (Med.), professor, chief medical officer, SPIN: 3327-2250, AuthorID: 693098

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



E. N. Fedotova
Clinical and Diagnostic Center "Zdorovie"
Russian Federation

Ekaterina N. Fedotova – biologist at the clinical laboratory diagnostics, SPIN: 3000-9183, AuthorID: 1109849

70/3 Dolomanovsky lane, Rostov-on-Don 344011, Russian Federation


Competing Interests:

Authors report no conflict of interest.



A. N. Shevchenko
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Alexey N. Shevchenko – Dr. Sci. (Med.), professor, head of the Department of Oncourology, SPIN: 2748-2638, AuthorID: 735424, ResearchID: Y-5387-2018, Scopus Author ID: 57192283096

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



S. M. Pakus
Clinical and Diagnostic Center "Zdorovie"
Russian Federation

Sergei M. Pakus – Cand. Sci. (Med.), urologist 

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



A. Yu. Maximov
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Alexei Yu. Maximov – Dr. Sci. (Med.), professor, deputy General Director for Advanced Scientific Research of the Department of Oncourology, SPIN: 7322-5589, AuthorID: 710705, Scopus Author ID: 56579049500

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



E. V. Filatova
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Elena V. Filatova – Cand. Sci. (Med.), oncologist, research fellow, SPIN: 7517-1549, AuthorID: 794870, Scopus Author ID 5719228349

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



I. A. Khomutenko
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Irina A. Khomutenko – Cand. Sci. (Med.), senior research fellow, SPIN: 5401-5810, AuthorID: 735408

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



Е. F. Komarova
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Ekaterina F. Кomarova – Professor of Russian Academy of Sciences, Dr. Sci. (Biol.), professor, senior research fellow, SPIN: 1094-3139, AuthorID: 348709, ResearcherID: T-4520-2019

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



N. K. Guskova
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Nailya K. Guskova – Cand. Sci. (Biol.), head of clinical diagnostic laboratory, SPIN: 5407-6285, AuthorID: 306979

Rostov-on-Don


Competing Interests:

Authors report no conflict of interest.



References

1. Kamalov AA, Samokhodskaya LM, Karpov VK, Okhobotov DA, Mamedov VN. Biomarkers of prostate cancer and potential of using ACE produced in prostate gland for diagnosis of prostate cancer and benign prostatic hyperplasia. Urology. 2019;(2):73-81. (In Russ.). https://doi.org/doi.org/10.18565/urology.2019.2.73-81

2. Duffy MJ. Biomarkers for prostate cancer: prostate-specific antigen and beyond. Clin Chem Lab Med. 2020 Feb 25;58(3):326-339. https://doi.org/10.1515/cclm-2019-0693

3. American Cancer Society. Cancer Facts & Figures, 2017. Available at: https://www.cancer.org/content/dam/cancer-org/research/ cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf, Accessed: 19.05.2021.

4. Toropovskiy AN, Nikitin AG, Pavlova ON, Viktorov DA. Perspectives of improvement of the diagnosis of prostate cancer based on analysis of PCA3 gene expression. Urology. 2019;(2):82-86. (In Russ.). https://doi.org/10.18565/urology.2019.2.82-86

5. Postma R, Schroder FH. Screening for prostate cancer. Eur J Cancer. 2005 Apr;41(6):825-833. https://doi.org/10.1016/j.ejca.2004.12.029

6. Stephan C, Vincendeau S, Houlgatte A, Cammann H, Jung K, Semjonow A. Multicenter evaluation of [-2]proprostate-specific antigen and the prostate health index for detecting prostate cancer. Clin Chem. 2013 Jan;59(1):306-314. https://doi.org/10.1373/clinchem.2012.195784

7. Ruzhanskaya AV, Yevgina SA, Skibo II. The practical application of marker -2propsa and health index of prostate phi in diagnostics of prostate cancer. Clinical Laboratory Diagnostics. 2014;59(1):4-8. (In Russ.).

8. Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bangma CH, et al. A multi center study of [-2]pro-prostate specific antigen com -bined 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. 2011 May;185(5):1650-1655. https://doi.org/10.1016/j.juro.2010.12.032

9. 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 Naive Men. J Urol. 2015 Jul;194(1):65-72. https://doi.org/10.1016/j.juro.2015.01.091

10. Loeb S, Sanda MG, Broyles DL, Shin SS, Bangma CH, Wei JT, et al. The prostate health index selectively identifies clinically significant prostate cancer. J Urol. 2015 Apr;193(4):1163-1169. https://doi.org/10.1016/j.juro.2014.10.121

11. White J, Shenoy BV, Tutrone RF, Karsh LI, Saltzstein DR, Harmon WJ, et al. Clinical utility of the Prostate Health Index (phi) for biopsy decision management in a large group urology practice seffing. Prostate Cancer Prostatic Dis. 2018 Apr;21(1):78-84. https://doi.org/10.1038/s41391-017-0008-7

12. Vickers A, Cronin A, Roobol M, Savage C, Peltola M, Pettersson K, et al. Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication. J Clin Oncol. 2010 May 20;28(15):2493-2498. https://doi.org/10.1200/JC0.2009.24.1968

13. Zappala SM, Dong Y, Linder V, Reeve M, Sjoberg DD, Mathur V, et al. The 4Kscore blood test accurately identifies men with aggressive prostate cancer prior to prostate biopsy with or without DRE information. Int J Clin Pract. 2017 Jun;71(6):e12943. https://doi.org/10.1111/ijcp.12943

14. McKiernan J, Donovan MJ, O'Neill 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 Jul 1;2(7):882-889. https://doi.org/10.1001/jamaoncol.2016.0097

15. Mottet N 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 Apr;71(4):618-629. https://doi.org/10.1016/j.eururo.2016.08.003

16. Carroll PR, Parsons JK, Andriole G, Bahnson RR, Castle EP, Catalona WJ, et al. NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016. J Natl Compr Canc Netw. 2016 May;14(5):509-519. https://doi.org/10.6004/jnccn.2016.0060

17. Suh SO, Chen Y, Zaman MS, Hirata H, Yamamura S, Shahryari V, et al. MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. Carcinogenesis. 2011 May;32(5):772-778. https://doi.org/10.1093/carcin/bgr036

18. Kanwal R, Plaga AR, Liu X, Shukla GC, Gupta S. MicroRNAs in prostate cancer: Functional role as biomarkers. Cancer Lett. 2017 Oct 28;407:9—20. https://doi.org/10.1016/j.canlet.2017.08.011

19. Sharma N, Baruah MM. The microRNA signatures: aberrantly expressed miRNAs in prostate cancer. Clin Transl Oncol. 2019 Feb;21(2):126-144. https://doi.org/10.1007/s12094-018-1910-8

20. 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 Jul;68(1):132-138. https://doi.org/10.1016/j.eururo.2014.07.034

21. Fradet Y, Saad F, Aprikian A, Dessureault J, Elhilali M, Trudel C, et al. uPM3, a new molecular urine test for the detection of prostate cancer. Urology. 2004 Aug;64(2):311-315. https://doi.org/10.1016/j.urology.2004.03.052

22. 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 Jul;31(5):566-571. https://doi.org/10.1016/j.urolonc.2011.04.001

23. Wang T, Qu X, Jiang J, Gao P, Zhao D, Lian X, et al. Diagnostic significance of urinary long non-coding PCA3 RNA in prostate cancer. Oncotarget. 2017 Aug 29;8(35):58577-58586. https://doi.org/10.18632/oncotarget.17272

24. 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 Feb;63(2):201-209. https://doi.org/10.1016/j.eururo.2012.07.030

25. 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 Jul;190(1):64-69. https://doi.org/10.1016/jjuro.2013.02.018

26. Bradley LA, Palomaki GE, Gutman S, Samson D, Aronson N. Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer. J Urol. 2013 Aug;190(2):389-398. https://doi.org/10.1016/jjuro.2013.02.005

27. Wei JT, Feng Z, Partin AW, Brown E, Thompson I, Sokoll L, et al. Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol. 2014 Dec 20;32(36):4066-4062. https://doi.org/10.1200/JCO.2013.52.8505

28. Whitman EJ, Groskopf J, Ali A, Chen Y, Blase A, Furusato B, et al. PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. J Urol. 2008 Nov;180(5):1975-1978. https://doi.org/10.1016/jjuro.2008.07.060

29. Turner AR, Feng J, Liu W. Prostate Cancer. Genomic and Personalized Medicine. 2nd Edn. Ch. 63. London: Academic Press. 2012, 733-741 p.

30. Li LC, Hsieh AC, Ruggero D. et al. Molecular basis of prostate cancer. Ch. 38. In: Mendelsohn J, Howley PM, Israel MA, et al. The molecular basis of cancer. 4th Edn. Philadelphia: Elsevier. 2015, 888 p.

31. Lamy P-J, Allory Y, Gauchez A-S, Asselain B, Beuzeboc P, de Cremoux P, et al. Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review. Eur Urol Focus. 2018 Dec;4(6):790-803. https://doi.org/10.1016/j.euf.2017.02.017

32. 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 Aug 3;3(94):94ra72. https://doi.org/10.1126/scitranslmed.3001970

33. Sanda MG, Feng Z, Howard DH, Tomlins SA, Sokoll LJ, Chan DW, et al. Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and Detection of Aggressive Prostate Cancer. JAMA Oncol. 2017 Aug 1;3(8):1085-1093. https://doi.org/10.1001/jamaoncol.20r7.0177

34. 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 Jul;70(1):45-53. https://doi.org/10.1016/j.eururo.2015.04.03

35. McLeod DG, Petrovics G. Re: Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and Detection of Aggressive Prostate Cancer. Eur Urol. 2018 Feb;73(2):301-302. https://doi.org/10.1016/j.eururo.2017.09.035

36. Rice KR, Chen Y, Ali A, Whitman EJ, Blase A, Ibrahim M, et al. Evaluation of the ETS-related gene mRNA in urine for the detection of prostate cancer. Clin Cancer Res. 2010 Mar 1;16(5):1572-1576. https://doi.org/10.1158/1078-0432.CCR-09-2191

37. 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 Nov;70(5):740-748. https://doi.org/10.1016/j.eururo.2016.04.012

38. Filatov MV, Landa SB, Pantina RA, Garmay YuP. Investigation of exosomes secreted by different normal and malignant cells in vitro and in vivo. Clinical laboratory diagnostics. 2010;(12):35-43. (In Russ.).

39. Nazimek K, Bryniarski K, Santocki M, Ptak W. Exosomes as mediators of intercellular communication: clinical implications. Pol Arch Med Wewn. 2015;125(5):370-380. https://doi.org/10.20452/pamw.2840

40. Malek AV, Bershteyn LM, Filatov MV, Belyayev AM. Exosomal intercellular communications system and its role in the process of metastatic dissemination. Oncology Questions. 2014;60(4):429-437. (In Russ.).

41. Drake RR, Kislinger T. The proteomics of prostate cancer exosomes. Expert Rev Proteomics. 2014 Apr;11(2):167-177. https://doi.org/10.1586/14789450.2014.890894

42. Sato-Kuwabara Y, Melo SA, Soares FA, Calin GA. The fusion of two worlds: non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications (Review). Int J Oncol. 2015 Jan;46(1):17-27. https://doi.org/10.3892/ijo.2014.2712

43. 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 Sep;76(12):1078-1087. https://doi.org/10.1002/pros.23191

44. Chan TA, Glockner S, Yi JM, Chen W, Van Neste L, Cope L, et al. Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis. PLoS Med. 2008 May 27;5(5):e114. https://doi.org/10.1371/journal.pmed.0050114

45. 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 Oct;192(4):1081-1087. https://doi.org/10.1016/j.juro.2014.04.013

46. Van Neste L, Herman JG, Otto G, Bigley JW, Epstein JI, Van Criekinge W. The epigenetic promise for prostate cancer diagnosis. Prostate. 2012 Aug 1;72(11):1248-1261. https://doi.org/10.1002/pros.22459

47. Wang W, Wang M, Wang L, Adams TS, Tian Y, Xu J. Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis. Sci Rep. 2014 May 23;4:5012. https://doi.org/10.1038/srep05012

48. Stewart GD, Van Neste L, Delvenne P, Delree 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 Mar;189(3):1110-1116. https://doi.org/10.1016/jjuro.2012.08.219

49. Van Den Eeden SK, Lu R, Zhang N, Quesenberry CP, Shan J, Han JS, et al. A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease. Eur Urol. 2018 Jan;73(1):129-138. https://doi.org/10.1016/j.eururo.2017.09.013

50. 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 Jul;68(1):123-131. https://doi.org/10.1016/j.eururo.2014.11.030

51. Mohler JL, Armstrong AJ, Bahnson RR, D'Amico AV, Davis BJ, Eastham JA, et al. Prostate Cancer, Version 1.2016. J Natl Compr Canc Netw. 2016 Jan;14(1):19-30. https://doi.org/10.6004/jnccn.2016.0004

52. Klein EA, Haddad Z, Yousefi K, Lam LLC, Wang Q, Choeurng V, et al. Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk. Urology. 2016 Apr;90:148-152. https://doi.org/10.1016/j.urology.2016.01.012

53. Nguyen PL, Haddad Z, Ross AE, Martin NE, Deheshi S, Lam LLC, et al. Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens. Eur Urol. 2017 Nov;72(5):845-852. https://doi.org/10.1016/j.eururo.2017.05.009


Supplementary files

Review

For citations:


Aboian I.A., Fedotova E.N., Shevchenko A.N., Pakus S.M., Maximov A.Yu., Filatova E.V., Khomutenko I.A., Komarova Е.F., Guskova N.K. Current biomarkers of prostate cancer. Research and Practical Medicine Journal. 2021;8(4):96-108. (In Russ.) https://doi.org/10.17709/2410-1893-2021-8-4-10

Views: 912


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-1893 (Online)