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

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.

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.

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.

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.