Construction of a m6A RNA Methylation Regulator-related Signature for Prognosis and Immune Response in Lung Adenocarcinoma

Abstract BackgroundN6-methyladenosine (m6A) RNA methylation is related to cancer pathogenesis and development. However, few studies have investigated the role of m6A regulator genes in lung adenocarcinoma (ADC).MethodsGene expressions with clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) database. We compared the expression of twenty m6A regulator genes between tumor and normal samples. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression model were used to derive a multi-gene signature. A signature-based nomogram was developed, and the prediction performance was validated by an exterior validation set (GSE72094). Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network and identify the hub genes. The association of m6A signature with immunity was examined.ResultsSeventeen differentially expressed genes were identified. A five-gene prognostic signature (IGF2BP1, IGF2BP2, HNRNPA2B1, METTL3, and HNRNPC) was determined, and demonstrated as an unfavorable prognostic factor. A signature-based nomogram was developed to predict each patient’s survival probability, and the nomogram was well calibrated and showed a satisfactory discrimination. Turquoise was identified as the most risk-related module, and genes in this module were enriched in the pathway of cell cycle. Six genes were determined as the hub genes. High-risk patients had significantly higher expression of PD-L1, higher tumor mutational burden (TMB), higher proportion of immune checkpoint blockade (ICB) response, and lower proportion of T cells CD8.ConclusionsIn summary, the signature-based nomogram is useful for survival prediction, and high-risk patients were more sensitive to the ICB therapy.