Comprehensive Analysis of Clinical Significance, Immune Infiltration and Biological Role of mA Regulators in Early-Stage Lung Adenocarcinoma.

Recent publications have revealed that N6-methyladenosine (mA) modification is critically involved in tumorigenesis and metastasis. However, the correlation of mA modification and immune infiltration in early-stage lung adenocarcinoma (LUAD) is still uncertain. We performed NMF clustering based on 23 mA regulators and identify three distinct mA clusters and three mA related genes clusters (mA cluster-R) in early-stage LUAD. The immune infiltrating levels were calculated using CIBERSORT, MCPcounter and ssGSEA algorithms. And we established the mA-predictive score to quantify mA modified phenotypes and predict immunotherapeutic responses. Based on the TME characteristics, different immune profiles were also identified among three mA gene-related clusters. And the mA-R-C2 was related to a favorable overall survival (OS), whereas mA-R-C3 had unfavorable overall survival. The mA-predictive score was built according to the expression levels of mA-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 mA modification is closely related to immune infiltration in early-stage LUAD, which also contributes to the development of more effective immunotherapy strategies.