Comprehensive Analysis of Clinical Significance, Immune Infiltration and Biological Role of m(6)A Regulators in Early-Stage Lung Adenocarcinoma

Recent publications have revealed that N6-methyladenosine (m(6)A) modification is critically involved in tumorigenesis and metastasis. However, the correlation of m(6)A modification and immune infiltration in early-stage lung adenocarcinoma (LUAD) is still uncertain. We performed NMF clustering based on 23 m(6)A regulators and identify three distinct m(6)A clusters and three m(6)A related genes clusters (m(6)A cluster-R) in early-stage LUAD. The immune infiltrating levels were calculated using CIBERSORT, MCPcounter and ssGSEA algorithms. And we established the m(6)A-predictive score to quantify m(6)A modified phenotypes and predict immunotherapeutic responses. Based on the TME characteristics, different immune profiles were also identified among three m(6)A gene-related clusters. And the m(6)A-R-C2 was related to a favorable overall survival (OS), whereas m(6)A-R-C3 had unfavorable overall survival. The m(6)A-predictive score was built according to the expression levels of m(6)A-related genes, and patients could be stratified into subgroups with low/high scores. Patients with high scores had poor overall survival, enhanced immune infiltration, high tumor mutation burden and increased level of somatic mutation. Besides, patients with high scores had unfavorable overall survival in the anti-PD-1 cohort, whereas the overall survival of high-score patients was better in the adoptive T cell therapy cohort. Our work highlights that m(6)A modification is closely related to immune infiltration in early-stage LUAD, which also contributes to the development of more effective immunotherapy strategies.