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

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 5'-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 5'-LTR in HERVW gene promoter was relatively lower in NSCLC than paracarcinoma 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.

Automated summary

In non-small cell lung cancer (NSCLC), syncytin-1 expression is significantly higher in tumor tissues compared to adjacent tissues, with lower expression in the 5-year survival group. Clinical stage and the percentage of syncytin-1 positive cells are identified as top risk factors for NSCLC patient survival differentiation. The methylation status of a specific site overlapping the Oct-1 binding site may play a role in epigenetic regulation of HERVW gene expression in NSCLC.