N6-methyladenosine (m6A) regulator expression pattern correlates with the immune landscape in lung adenocarcinoma

Lung adenocarcinoma is the leading cause of tumor-related death. The tumor microenvironment (TME) may determine anti-tumor treatment responses. We focused on 23 m6A regulators, and analyzed m6A regulator expression patterns in 995 lung adenocarcinoma samples collected from 7 publicly available datasets. Two m6A clusters were identified, wherein gene clusters and m6A score were generated using unsupervised clustering and principal component analysis based on differentially expressed genes with prognostic significance. Further, three independent datasets from TCGA-LUAD and GEO were employed to validate the impact of m6A signatures and score. We found that m6A cluster 1 with high m6A score was associated with an inflamed TME, higher neoantigen and tumor mutation burden and improved response to immunotherapy. However, anti-tumor immunity cells were exhausted in high m6A score patients; thus, the prognosis of these patients was poor. Elucidation of m6A regulator expression pattern may facilitate the development of effective treatment strategies for lung adenocarcinoma.