Prognostic Analysis of Lung Adenocarcinoma Based on DNA Methylation Regulatory Factor Clustering

There is a known link between DNA methylation and cancer immunity/immunotherapy; however, the effect of DNA methylation on immunotherapy in lung adenocarcinoma (LUAD) remains to be elucidated. In the current study, we aimed to screen key markers for prognostic analysis of LUAD based on DNA methylation regulatory factor clustering. We classified LUAD using the NMF clustering method, and as a result, we obtained 20 DNA methylation regulatory genes. These 20 regulatory genes were used to determine the pattern of DNA methylation regulation, and patients were grouped for further analysis. The risk score model was analyzed in the TCGA dataset and an external validation set, and the correlation between the risk score and DNA methylation regulatory gene expression was explored. We analyzed the correlation between the prognostic model and immune infiltration and checkpoints. Finally, we analyzed the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions of the prognosis model and established the nomogram model and decision tree model. The survival analyses of ClusterA and ClusterB were significantly different. Survival analysis showed that patients with a high risk score had a poor prognosis. Survival models (tobacco, T, N, M, stage, sex, age, status, and risk score) were abnormally correlated with T cells and macrophages. The higher the risk score associated with smoking was and the higher the stage was, the more severe the LUAD and the more maladjusted the immune system were. Immune infiltration and abnormal expression of immune checkpoint genes in the prognostic model of LUAD were associated with the risk score. The prognostic models were mainly enriched in the cell cycle and DNA replication. Characterization of DNA methylation regulatory patterns is helpful to improve our understanding of the immune microenvironment in LUAD and to guide the development of a more personalized immunotherapy strategy in the future.