M5C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in lung adenocarcinoma

Transl Lung Cancer Res. 2021 May;10(5):2172-2192. doi: 10.21037/tlcr-21-351.

Abstract

Background: In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m5C) in the tumor microenvironment (TME) and immunotherapy response remains unclear.

Methods: Based on 11 m5C regulators, we evaluated the m5C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m5C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m5C modification pattern of individual LUAD patients.

Results: Two m5C methylation modification patterns were identified according to 11 m5C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m5C phenotype were screened. Patients were divided into three different gene cluster subtypes based on these genes, which had different TME immune cell infiltration and prognosis characteristics. The m5C score was constructed to quantify the m5C modification pattern of individual LUAD patients. We found that the high m5C score group had a better prognosis. The role of the m5C score in predicting prognosis was also verified in the dataset GSE31210.

Conclusions: Our study revealed that m5C modification played a significant role in TME regulation of LUAD. Investigation of the m5C regulation mode may have some implications for tumor immunotherapy in the future.

Keywords: M5C; immunotherapy; lung adenocarcinoma (LUAD); tumor microenvironment (TME).