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

BACKGROUND: In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m(5)C) in the tumor microenvironment (TME) and immunotherapy response remains unclear. METHODS: Based on 11 m(5)C regulators, we evaluated the m(5)C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m(5)C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m(5)C modification pattern of individual LUAD patients. RESULTS: Two m(5)C methylation modification patterns were identified according to 11 m(5)C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m(5)C 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 m(5)C score was constructed to quantify the m(5)C modification pattern of individual LUAD patients. We found that the high m(5)C score group had a better prognosis. The role of the m(5)C score in predicting prognosis was also verified in the dataset GSE31210. CONCLUSIONS: Our study revealed that m(5)C modification played a significant role in TME regulation of LUAD. Investigation of the m(5)C regulation mode may have some implications for tumor immunotherapy in the future.