Roles of m6A regulators in shaping methylation patterns and tumor microenvironment immune infiltration in colorectal...

Recent studies have demonstrated that immune responses are subject to epigenetic regulation. However, the functional roles of RNA N6-methyladenosine (m6A) modification in infiltrating cells within the tumor microenvironment (TME) remain incompletely understood. To systematically characterize m6A modification patterns, we conducted a comprehensive analysis across 1,195 colorectal cancer samples, focusing on 27 m6A regulators. We further associated the three identified modification patterns with the characteristics of immune cell infiltration in the TME. To quantify m6A modification patterns at the individual tumor level, we developed an m6A score using principal component analysis (PCA). Analysis of immune cell infiltration in the TME revealed that the three distinct m6A modification patterns were significantly associated with three tumor immune phenotypes: immune-excluded, immune-inflamed, and immune-desert. Furthermore, univariate and multivariate Cox regression analyses indicated that the m6A score served as an independent and reliable prognostic biomarker for colorectal cancer (CRC) patients. Collectively, these findings suggest that m6A modification is associated with immune modulation and correlates with TME heterogeneity. Characterization of m6A modification patterns in CRC patients may enhance our understanding of immune cell infiltration within the TME and inform immunotherapeutic strategies.