Comprehensive Analysis of Immune Infiltrates and Prognosis of m6A RNA Methylation Regulators in Lung Cancer

OBJECTIVE To preliminarily explore the potential role and mechanism of N6-methyl-adenosine(m6A) methylation regulators in the immune microenvironment of lung cancer. METHODS The correlation of immune infiltrates and prognosis of m6A RNA methylation regulators in lung cancer was comprehensively analyzed by bioinformatics, based on TCGA database. RESULTS Some m6A RNA methylation regulators were differentially expressed in lung squamous carcinoma(LUSC) and lung adenocarcinoma(LUAD). However, ALKBH5 was significantly high expressed only in LUSC, METTL3 and YTHDF3 were significantly high expressed only in LUAD, and HNRNPA2B1 was associated with the expression of YTHDC1 in LUSC and RBM15 in LUAD. By consistent clustering of 18 m6A methylation regulators, it was found that there was no statistically significant difference of the overall survival(OS) among different subtypes of LUSC. In LUAD, there was no significant difference in the expression of PD-1 and PD-L1 between cancer and adjacent tissues, and there was also no significant correlation with m6A methylation regulators. Cluster analysis revealed that m6A methylation regulators played an important role in the immune microenvironment of LUAD, in which the expression of PD-L1 decreased and the infiltration of immune cells was higher in Cluster 2, but the OS was longer than that in Cluster 1. Cluster 2 was more correlated with dendritic cell resting, mast cell resting, T cells gamma delta. The short OS of Cluster 1 may be related to the G2M checkpoint, E2F pathway, MYC pathway, MTORC1 pathway, Wnt/beta-catenin pathway, as well as the higher level of dendritic cells activated, macrophages M1 and T cells follicular helper. Univariate Cox analysis showed that four methylated binding proteins were associated with prognosis, IGF2BP3, HNRNPA2B1 and IGF2BP2 were risk factors and YTHDF2 was protection factor. CONCLUSION m6A RNA methylation regulators are closely related to the immune infiltration and prognosis of LUAD.