Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma

Abstract

Background: N6-methyladenosine (m⁶A) RNA modification is vital for cancers because methylation can alter gene expression and even affect some functional modification. Our study aimed to analyze m⁶A RNA methylation regulators and m⁶A-related genes to understand the prognosis of early lung adenocarcinoma.Methods: The relevant datasets were utilized to analyze 21 m⁶A RNA methylation regulators and 5,486 m⁶A-related genes in m⁶Avar. Univariate Cox regression analysis, random survival forest analysis, Kaplan–Meier analysis, Chi-square analysis, and multivariate cox analysis were carried out on the datasets, and a risk prognostic model based on three feature genes was constructed.Results: Respectively, we treated GSE31210 (n = 226) as the training set, GSE50081 (n = 128) and TCGA data (n = 400) as the test set. By performing univariable cox regression analysis and random survival forest algorithm in the training group, 218 genes were significant and three prognosis-related genes (ZCRB1, ADH1C, and YTHDC2) were screened out, which could divide LUAD patients into low and high-risk group (P < 0.0001). The predictive efficacy of the model was confirmed in the test group GSE50081 (P = 0.0018) and the TCGA datasets (P = 0.014). Multivariable cox manifested that the three-gene signature was an independent risk factor in LUAD. Furthermore, genes in the signature were also externally validated using the online database. Moreover, YTHDC2 was the important gene in the risk score model and played a vital role in readers of m⁶A methylation.Conclusion: The findings of this study suggested that associated with m⁶A RNA methylation regulators and m⁶A-related genes, the three-gene signature was a reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target.