Molecular survey on Merkel cell polyomavirus in patients with colorectal cancer
Background: Merkel cell polyomavirus (MCV) has been associated with Merkel cell carcinoma (MCC) in humans, and its role in other human cancers is under investigation. The aim of this study was to investigate MCV genome infection in patients with colorectal cancer (CRC).
Methods: This retrospective, case-control study used archived formalin-fixed, paraffin-embedded (FFPE) tissue samples from colorectal cancer patients (cases) and matched healthy subjects (controls) diagnosed by an expert pathologist from hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran from 2011 to 2016. After DNA extraction with a QIAamp® DNA FFPE Tissue Kit, real-time polymerase chain reaction (PCR) was used for diagnosis. A positive control was produced by cloning with the Generay Biotechnology system. SPSS v.22 was used for analysis of demographic variables.
Results: There were 157 participants included in the study: 66 were cases and 91 were controls. Their mean ages (±SD) were 59.35±14.48 and 57.21±14.66, respectively. The proportion of males was 57.6% in the case group and 57.1% in the control group. None of the samples were positive for MCV expression by real-time PCR assay. Association was detected between males with CRC and tumor location in the rectum and between males with CRC and the mucinous tumor type.
Conclusion: None of the tissues from the CRC or non-cancerous control groups were positive for MCV genome infection, although a low viral load, the sample type, or the method of use should not be neglected. Further studies are recommended to obtain more comprehensive results.
Koochak A, Rakhshani N, Karbalaie Niya MH, Tameshkel FS, Sohrabi MR, Babaee MR, et al. Mutation analysis of KRAS and BRAF genes in metastatic colorectal cancer: a first large scale study from Iran. Asian Pac J Cancer Prev. 2016;17(2):603–8. https://doi.org/10.7314/APJCP.2016.17.2.603
Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–93. https://doi.org/10.3322/caac.21395
Mesri EA, Feitelson MA, Munger K. Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe. 2014;15(3):266–82. https://doi.org/10.1016/j.chom.2014.02.011
Chiocca EA, Rabkin SD. Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res. 2014;2(4):295–300. https://doi.org/10.1158/2326-6066.CIR-14-0015
Chen H, Chen XZ, Waterboer T, Castro FA, Brenner H. Viral infections and colorectal cancer: a systematic review of epidemiological studies. Int J Cancer. 2015;137(1):12–24. https://doi.org/10.1002/ijc.29180
Teklemariam AD, Geleta G, Tassew A. A review on gene involved in cancer development and oncogenic viruses. Afr J Basic Appl Sci. 2015;7(4):223–32. https://doi.org/10.5829/idosi.ajbas.2015.7.4.1148
MacDonald M, You J. Merkel cell polyomavirus: A new DNA virus associated with human cancer. Infectious agents associated cancers: Epidemiology and Molecular Biology: Springer; 2017. p. 35–56. https://doi.org/10.1007/978-981-10-5765-6_4
Scadden JR, Sharif A, Skordilis K, Borrows R. Polyoma virus nephropathy in kidney transplantation. World J Transplant. 2017;7(6):329–38. https://doi.org/10.5500/wjt.v7.i6.329
Salehi-Vaziri M, Sadeghi F, Alamsi-Hashiani A, Haeri H, Monavari SH, Keyvani H. Merkel cell polyomavirus and human papillomavirus infections in cervical disease in Iranian women. Arch Virol. 2015;160(5):1181–7. https://doi.org/10.1007/s00705-015-2368-4
Loutfy SA, Moneer MM, Salem SE, El-Moniem Abada EA, El-Moniem Ahmed EA, Ibrahim LH, et al. Polyomavirus infections and its clinical relevance in cancer patients: a prospective study. J Infect Public Health. 2017;10(1):22–30. https://doi.org/10.1016/j.jiph.2016.01.008
Arora R, Chang Y, Moore PS. MCV and Merkel cell carcinoma: a molecular success story. Curr Opin Virol. 2012;2(4):489–98. https://doi.org/10.1016/j.coviro.2012.05.007
Ripple MJ, Parker Struckhoff A, Trillo-Tinoco J, Li L, Margolin DA, McGoey R, et al. Activation of c-Myc and Cyclin D1 by JCV T-Antigen and β-catenin in colon cancer. PLoS One. 2014;9(9):e106257. https://doi.org/10.1371/journal.pone.0106257
Ramamoorthy S, Devaraj B, Miyai K, Luo L, Liu YT, Boland CR, et al. John Cunningham virus T-antigen expression in anal carcinoma. Cancer. 2011;117(11):2379–85. https://doi.org/10.1002/cncr.25793
Laghi L, Randolph AE, Chauhan DP, Marra G, Major EO, Neel JV, et al. JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci U S A. 1999;96(13):7484–9. https://doi.org/10.1073/pnas.96.13.7484
Mou X, Chen L, Liu F, Lin J, Diao P, Wang H, et al. Prevalence of JC virus in Chinese patients with colorectal cancer. PLoS One. 2012;7(5):e35900. https://doi.org/10.1371/journal.pone.0035900
Kisseljov FL, Vinokurova SV, Kisseljova NP. Novel human DNA viruses and their putative associations with human diseases. Mol Biol (Mosk). 2016;50(4):551–66. https://doi.org/10.1134/S0026893316040063
Sadeghi F, Salehi-Vaziri M, Alizadeh A, Ghodsi SM, Bokharaei-Salim F, Fateh A, et al. Detection of Merkel cell polyomavirus large T-antigen sequences in human central nervous system tumors. J Med Virol. 2015;87(7):1241–7. https://doi.org/10.1002/jmv.24178
Campello C, Comar M, D'Agaro P, Minicozzi A, Rodella L, Poli A. A molecular case-control study of the Merkel cell polyomavirus in colon cancer. J Med Virol. 2011;83(4):721–4. https://doi.org/10.1002/jmv.22004
Katano H, Ito H, Suzuki Y, Nakamura T, Sato Y, Tsuji T, et al. Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi's sarcoma. J Med Virol. 2009;81(11):1951–8. https://doi.org/10.1002/jmv.21608
Loyo M, Guerrero-Preston R, Brait M, Hoque MO, Chuang A, Kim MS, et al. Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission. Int J Cancer. 2010;126(12):2991–6. https://doi.org/10.1002/ijc.24737
Eftekhaar NS, Karbalaie Niya MH, Izadi F, Teaghinezhad-S S, Keyvani H. Human papillomavirus (HPV) genotype distribution in patients with recurrent respiratory papillomatosis (RRP) in Iran. Asian Pac J Cancer Prev. 2017;18(7):1973–6. https://doi.org/10.1016/j.rmed.2017.07.022
Karbalaie Niya MH, Safarnezhad Tameshkel F, Panahi M, Bokharaei Salim F, Monavari SH, Keyvani H. Human papillomavirus investigation in head and neck squamous cell carcinoma: initial report from the low risk HPV types associations. Asian Pac J Cancer Prev. 2017;18(9):2573–9. https://doi.org/10.22034/APJCP.2017.18.9.2573
Sadeghi F, Ghanadan A, Salehi-Vaziri M, Salim FB, Monavari SH, Keyvani H. Merkel cell polyomavirus infection in a patient with merkel cell carcinoma: a case report. Jundishapur J Microbiol. 2015;8(3):e17849. https://doi.org/10.5812/jjm.17849
Hamza H, Hamza IA. Oncogenic papillomavirus and polyomavirus in urban sewage in Egypt. Sci Total Environ. 2018;610–611:1413–20. https://doi.org/10.1016/j.scitotenv.2017.08.218
zur Hausen H. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer. Int J Cancer. 2012;130(11):2475–83. https://doi.org/10.1002/ijc.27413
Moens U, Rasheed K, Abdulsalam I, Sveinbjørnsson B. The role of Merkel cell polyomavirus and other human polyomaviruses in emerging hallmarks of cancer. Viruses. 2015;7(4):1871–901. https://doi.org/10.3390/v7041871
Baez CF, Brandão Varella R, Villani S, Delbue S. Human polyomaviruses: the battle of large and small tumor antigens. Virology (Auckl). 2017;8:1–12. https://doi.org/10.1177/1178122X17744785
Yahyapour Y, Sadeghi F, Alizadeh A, Rajabnia R, Siadati S. Detection of Merkel cell polyomavirus and human papillomavirus in esophageal squamous cell carcinomas and non-cancerous esophageal samples in Northern Iran. Pathol Oncol Res. 2016;22(4):667–72. https://doi.org/10.1007/s12253-016-0048-7
Mohebbi E, Noormohamadi Z, Sadeghi-Rad H, Sadeghi F, Yahyapour Y, Vaziri F, et al. Low viral load of Merkel cell polyomavirus in Iranian patients with head and neck squamous cell carcinoma: is it clinically important? J Med Virol. 2018;90(2):344–50. https://doi.org/10.1002/jmv.24953
Reza MA, Reza MH, Mahdiyeh L, Mehdi F, Hamid ZN. Evaluation frequency of Merkel cell polyoma, epstein-Barr and mouse mammary tumor viruses in patients with breast cancer in Kerman, southeast of Iran. Asian Pac J Cancer Prev. 2015;16(16):7351–7. https://doi.org/10.7314/APJCP.2015.16.16.7351
Bhatia S, Afanasiev O, Nghiem P. Immunobiology of Merkel cell carcinoma: implications for immunotherapy of a polyomavirus-associated cancer. Current Oncol Rep. 2011;13(6):488–97. https://doi.org/10.1007/s11912-011-0197-5
Kean JM, Rao S, Wang M, Garcea RL. Seroepidemiology of human polyomaviruses. PLoS Pathog. 2009;5(3):e1000363. https://doi.org/10.1371/journal.ppat.1000363
Touzé A, Le Bidre E, Laude H, Fleury MJ, Cazal R, Arnold F, et al. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome. J Clin Oncol. 2011;29(12):1612–9. https://doi.org/10.1200/JCO.2010.31.1704
Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, et al. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer. 2009;125(6):1250–6. https://doi.org/10.1002/ijc.24509
Nicol JT, Robinot R, Carpentier A, Carandina G, Mazzoni E, Tognon M, et al. Age-specific seroprevalences of Merkel cell polyomavirus, human polyomaviruses 6, 7, and 9, and trichodysplasia spinulosa-associated polyomavirus. Clin Vaccine Immunol. 2013;20(3):363–8. https://doi.org/10.1128/CVI.00438-12
Viscidi RP, Rollison DE, Sondak VK, Silver B, Messina JL, Giuliano AR, et al. Age-specific seroprevalence of Merkel cell polyomavirus, BK virus, and JC virus. Clin Vaccine Immunol. 2011;18(10):1737–43. https://doi.org/10.1128/CVI.05175-11
Baez CF, da Rocha WM, Afonso LA, Carestiato FN, Guimarães MA, Cavalcanti SM, et al. First report of three major oncogenic viruses: human papillomavirus, epstein-barr virus and merkel cell polyomavirus in penile cancer. J Infect Dis Ther. 2015;3(5):233. https://doi.org/10.4172/2332-0877.1000233
Copyright (c) 2018 Mohammad Hadi Karbalaie Niya, Fahimeh Safarnezhad Tameshkel, Mahdi Alemrajabi, Mahsa Taherizadeh, Mohsen Keshavarz, Mohsen Rezaee, Hossein Keyvani
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.