An N6-Methyladenosine-Related Gene Set Variation Score as a Prognostic Tool for Lung Adenocarcinoma.

Abstract

N6-methyladenosine (m6A) is the most prevalent type of RNA modification, and we hypothesized that patterns of m6A-related genes may be useful for estimating risk of lung adenocarcinoma (LUAD). An m6A-related gene set variation score (m6A-GSVS) was generated using RNA-sequencing data from LUAD patients in The Cancer Genome Atlas (TCGA). We investigated the association of m6A-GSVS with stemness, tumor mutational burden (TMB), expression of three immune checkpoints, levels of tumor-infiltrating lymphocytes (TILs), and patient prognosis. We found that m6A-GSVS was higher in LUAD than in healthy lung tissue, and it strongly correlated with stemness and TMB. Activated CD4 + T cells were more numerous in LUAD samples that had higher m6A-GSVS than in those with lower scores. Biological processes and pathways, including “Cell cycle,” “DNA replication,” and “RNA degradation,” were significantly enriched in samples with high scores. Furthermore, m6A-GSVS was an independent prognostic indicator in LUAD. In conclusion, we proposed an m6A-GSVS in LUAD. It is a putative indicator for evaluating the ability to RNA m6A, an independent prognostic indicator and associated with tumor stemness.