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Epigenetic modifications, especially N 6 -methyladenosine (m 6 A) modification, play a key role in tumor microenvironment (TME) infiltration. However, the regulatory role of m 6 A modification in the TME of lung adenocarcinoma (LUAD) remains unclear. A total of 2506 patients with LUAD were included in the analysis and divided into different groups according to distinct m 6 A modification-related patterns based on 23 m 6 A regulators. A comprehensive analysis was performed to explore TME infiltration in different m 6 A modification-related patterns. Principal component analysis was performed to obtain the m 6 Ascore and to quantify m 6 A modification-related patterns in different individuals. Three distinct m 6 A modification-related patterns were identified by 23 m 6 A regulators. The pathway enrichment analysis showed that m 6 Acluster-A was associated with immune activation; m 6 Acluster-B was associated with carcinogenic activation; m 6 Acluster-C was prominently related to substance metabolism. M 6 Acluster-A was remarkably rich in TME-infiltrating immune cells and patients with this pattern showed a survival advantage. The m 6 Ascore could predict TME infiltration, tumor mutation burden (TMB), the effect of tumor immunotherapy, and the prognosis of patients in LUAD. High m 6 Ascore was characterized by increased TME infiltration, reduced TMB, and survival advantage. Patients with a high m 6 Ascore exhibited significantly improved clinical response to anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA4) immunotherapy. This study explored the regulatory mechanisms of TME infiltration in LUAD. The comprehensive analysis of m 6 A modification-related patterns may contribute to the development of individualized immunotherapy and the improvement of the overall effectiveness of immunotherapy for LUAD patients.

Multi-omics analysis of m6A modification-related patterns based on m6A regulators and tumor microenvironment infiltration in lung adenocarcinoma