Human BKV large T genome detection in prostate cancer and benign prostatic hyperplasia tissue samples by nested PCR: A case-control study

Document Type : Original article

Authors

1 Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Community Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pathology, Mashhad Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Human BK polyomavirus (BKPyV) is a latent infectious agent in the genitourinary tract associated with hemorrhagic cystitis and nephropathy. This virus can be a risk factor for various human malignancies, including prostate cancer (PCa). It may contribute to prostate cancer development, as it demonstrates oncogenic properties by encoding oncoproteins. This study assessed the prevalence of this virus in benign and malignant prostate tissues. Between 2009 and 2019, 49 formalin-fixed paraffin-embedded (FFPE) PCa and 49 benign prostatic hyperplasia (BPH) samples were gathered from the pathology department of a tertiary care university hospital. They were used as cases and controls, respectively. After deparaffinization and DNA extraction, nested PCR was applied to identify the BKPyVgp5 gene (LTAg) using inner and outer primers. The nested PCR showed a 278-bp bond corresponding to the BKPyVgp5 genome (LTAg) in 53.1% (26/49) of PCa and 14.3% (7/49) of BPH (p<0.001). The presence of BKV was significantly associated with an increased risk of PCa development (OR=6.78, 95% CI=2.55–18.02, p<0.001). The BKV LTAg gene was significantly more prevalent in PCa samples than in BPH samples. These results demonstrate the presence of the virus in prostate cancer tissues.

Keywords


  1. Wang L, Lu B, He M, Wang Y, Wang Z, Du L. Prostate cancer incidence and mortality: global status and temporal trends in 89 countries from 2000 to 2019. Front Public Health 2022;10:811044.
  2. American Cancer Society. Cancer facts & figures 2022. Atlanta: American Cancer Society; 2022;2022.
  3. Hassanipour S, Fathalipour M, Salehiniya H. The incidence of prostate cancer in Iran: a systematic review and meta-analysis. Prostate Int 2018;6:41-45.
  4. Khazaei S, Rezaeian S, Ayubi E, Gholamaliee B, Pishkuhi MA, Mansori K, Nematollahi S, Sani M, Mansouri Hanis S. Global prostate cancer incidence and mortality rates according to the human development index. Asian Pac J Cancer Prev 2016;17:3791-3796.
  5. Pakzad R, Rafiemanesh H, Ghoncheh M, Sarmad A, Salehiniya H, Hosseini S, Sepehri Z, Afshari-Moghadam A. Prostate cancer in Iran: trends in incidence and morphological and epidemiological characteristics. Asian Pac J Cancer Prev 2016;17:839-843.
  6. Kimura T, Egawa S. Epidemiology of prostate cancer in Asian countries. Int J Urol 2018;25: 524-531.
  7. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007;7:256-269.
  8. Kirby RS, McConnell JD, Fitzpatrick JM, Roehrborn CG, Boyle P. Textbook of benign prostatic hyperplasia: CRC Press; 2004.
  9. Speakman M, Kirby R, Doyle S, Ioannou C. Burden of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH)–focus on the UK. BJU Int 2015; 115:508-519.
  10. Antonic V, Stojadinovic A, Kester KE, Weina PJ, Brücher BL, Protic M, Avital I, Izadjoo M. Significance of infectious agents in colorectal cancer development. J Cancer 2013;4: 227-240.
  11. Morales-Sánchez A, Fuentes-Pananá EM. Human viruses and cancer. Viruses 2014;6:4047-4079.
  12. Krump NA, You J. Molecular mechanisms of viral oncogenesis in humans. Nat Rev Microbiol 2018;16:684-698.
  13. Prado JCM, Monezi TA, Amorim AT, Lino V, Paladino A, Boccardo E. Human polyomaviruses and cancer: an overview. Clinics (Sao Paulo) 2018;73(suppl 1):e558s.
  14. Izi S, Youssefi M, Mohammadian Roshan N, Azimian A, Amel Jamehdar S, Zahedi Avval F. Higher detection of JC polyomavirus in colorectal cancerous tissue after pretreatment with topoisomerase I enzyme; colorectal tissue serves as a JCPyV persistence site. Exp Mol Pathol 2021;123:104687.
  15. Robles C, Viscidi R, Malats N, Silverman DT, Tardon A, Garcia-Closas R, Serra C, Carrato A, Herranz J, Lloreta J, Rothman N, Real FX, De Sanjose S, Kogevinas M. Bladder cancer and seroreactivity to BK, JC and Merkel cell polyomaviruses: the Spanish bladder cancer study. Int J Cancer 2013;133:597-603.
  16. Levican J, Acevedo M, León O, Gaggero A, Aguayo F. Role of BK human polyomavirus in cancer. Infect Agent Cancer 2018;13:12.
  17. Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis 2003;3:611-623.
  18. Jiang M, Abend JR, Johnson SF, Imperiale MJ. The role of polyomaviruses in human disease. Virology 2009;384:266-273.
  19. Theile M, Grabowski G. Mutagenic activity of BKV and JCV in human and other mammalian cells. Arch Virol 1990;113:221-233.
  20. Seif I, Khoury G, Dhar R. The genome of human papovavirus BKV. Cell 1979;18:963-977.
  21. Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol 1992;23:273-279.
  22. Ferrante P, Caldarelli-Stefano R, Omodeo-Zorini E, Vago L, Boldorini R, Costanzi G. PCR detection of JC virus DNA in brain tissue from patients with and without progressive multifocal leukoencephalopathy. J Med Virol 1995;47:219-225.
  23. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-249.
  24. Krajewski W, Kamińska D, Poterek A, Małkiewicz B, Kłak J, Zdrojowy R, Janczak D. Pathogenicity of BK virus on the urinary system. Cent European J Urol 2020;73:94-103.
  25. Elyasi MM, Makvandi M, Ranjbari N, Latifi SM, Kaydani GA, Shamloo MBB. Prevalence of human polyomavirus BK virus in prostate cancer patients and benign prostatic hyperplasia: A cross-sectional study on prostate patients referred to Imam Khomeini hospital in Ahvaz between 2015 and 2017. Jundishapur J Microbiol 2021;14:e115388.
  26. Gorish BMT, Ournasseir MEH, Shammat IM. A correlation study of BK Polyoma Virus infection and prostate cancer among Sudanese patients-immunofluorescence and molecular based case-control study. Infect Agent Cancer 2019;14:25.
  27. Das D, Wojno K, Imperiale MJ. BK virus as a cofactor in the etiology of prostate cancer in its early stages. J Virol 2008;82:2705-2714.
  28. Malekshahi SS, Yavarian J, Salehi R, Babaei F, Ahmadi SA, Ghavami N, Naseri M, Hosseini M, Mokhtari-Azad T, Shafiei-Jandaghi NZ. Epstein-Barr and BK virus in cancerous and noncancerous prostate tissue. Future Virol 2020;15:13-17.
  29. Lau SK, Lacey SF, Chen YY, Chen WG, Weiss LM. Low frequency of BK virus in prostatic adenocarcinomas. Apmis. 2007;115:743-749.
  30. Arabshahi S. Detection of polyomaviral large T antigen in benign prostatic hyperplasia and prostate carcinoma tissues. J Krishna Inst Med Sci Univ 2015;4:28-33.