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Correlation Between Promoter Hypomethylation and Increased Expression of Syncytin-1 in Non-Small Cell Lung Cancer

Authors Fu Y, Zhuang X, Xia X, Li X, Xiao K, Liu X

Received 27 November 2020

Accepted for publication 19 February 2021

Published 19 March 2021 Volume 2021:14 Pages 957—965

DOI https://doi.org/10.2147/IJGM.S294392

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Scott Fraser


Yang Fu,1 Xuewei Zhuang,2,3 Xiyan Xia,4 Xiaohui Li,3 Ke Xiao,3 Xiaojing Liu3

1Department of Reproductive Medicine Center, Jinan Maternity and Child Care Hospital, Jinan, 250001, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250031, People’s Republic of China; 3Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 4Department of Microbial Immune, Jinan Vocational College of Nursing, Jinan, 250012, People’s Republic of China

Correspondence: Xuewei Zhuang Tel +86-531-81656669
Fax +86-531-86927544
Email [email protected]

Introduction: Syncytin-1 is a human endogenous retroviral (HERVW) envelope protein, which has been implicated in trophoblast and cancer cell fusions as well as in immunomodulatory functions. We investigated syncytin-1 expression and promoter methylation in non-small cell lung cancer (NSCLC) and the adjacent, para-carcinoma tissues. In addition, the correlation to patient survival differentiation of between 5-year survival and death group was analyzed.
Methods: Survival ratio was calculated by Kaplan-Meier survival curve. Death risk assessment was executed by Cox risk regression model. The 5ʹ-LTR methylation level of HERVW promoter was detected by EpiTYPER method.
Results: Syncytin-1 expression in NSCLC tissue was found to be significantly higher than in para-carcinoma tissues. Moreover, the 5-year survival group has a lower syncytin-1 expression than the death group. Clinical stage and the percentage of syncytin-1 positive cells were top risk factors according to Cox ratio risk regression model analysis. While the methylation level of the 5ʹ-LTR in HERVW gene promoter was relatively lower in NSCLC than para-carcinoma tissues, the methylation status of a CpG-2 site overlapping the Oct-1 binding site was found to be an important element potentially involved in the epigenetic regulation of HERVW gene expression.
Conclusion: These findings suggest that syncytin-1 could be a biomarker for the diagnosis/prognosis of NSCLC, and further studies are required to elucidate the exact role of syncytin-1 in the development of NSCLC as well as the underlying molecular mechanism for syncytin-1 function and regulation.

Keywords: non-small cell lung cancer, syncytin-1, epigenetic regulation, prognosis, DNA methylation

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