The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissu
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RESEARCH ARTICLE
Open Access
The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue Marzieh Rezaei1, Shayan Mostafaei2,3, Amir Aghaei1, Nayyerehalsadat Hosseini4, Hassan Darabi4, Majid Nouri5, Ashkan Etemadi6, Andrew O’. Neill7, Javid Sadri Nahand8, Hamed Mirzaei9, Seamas C. Donnelly7, Mohammad Doroudian7,10* and Mohsen Moghoofei11,12*
Abstract Background: Lung cancer is a leading cause of cancer morbidity and mortality worldwide. Several studies have suggested that Human papillomavirus (HPV) infection is an important risk factor in the development of lung cancer. In this study, we aim to address the role of HPV in the development of lung cancer mechanistically by examining the induction of inflammation and epithelial-mesenchymal transition (EMT) by this virus. Methods: In this case-control study, tissue samples were collected from 102 cases with lung cancer and 48 controls. We examined the presence of HPV DNA and also the viral genotype in positive samples. We also examined the expression of viral genes (E2, E6 and E7), anti-carcinogenic genes (p53, retinoblastoma (RB)), and inflammatory cytokines in HPV positive cases. Results: HPV DNA was detected in 52.9% (54/102) of the case samples and in 25% (12/48) of controls. A significant association was observed between a HPV positive status and lung cancer (OR = 3.37, 95% C.I = 1.58–7.22, P = 0.001). The most prevalent virus genotype in the patients was type 16 (38.8%). The expression of p53 and RB were decreased while and inflammatory cytokines were increased in HPV-positive lung cancer and HPV-positive control tissues compared to HPV-negative lung cancer and HPV-negative control tissues. Also, the expression level of E-cad and PTPN-13 genes were decreased in HPV- positive samples while the expression level of SLUG, TWIST and N-cad was increased in HPV-positive samples compared to negative samples. Conclusion: Our study suggests that HPV infection drives the induction of inflammation and EMT which may promote in the development of lung cancer. Keywords: Human papilloma virus, Lung Cancer, Tumour development, Inflammatory cytokines, Epithelialmesenchymal transition (EMT)
* Correspondence: [email protected]; [email protected] 7 Department of Medicine, Trinity Centre, Tallaght University Hospital, Dublin 24, Ireland 11 Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, PO Box 6716777816, Razi Blvd, Kermanshah, Iran Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative C
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