Identification of N6-Methyladenosine-Related Gene Based Prognostic Signature to Predict Survival and Potential Therapeutic Drugs in Glioma

Abstract

N6-methyladenosine (m6A) modification is one of the most abundant RNA modification methods in the eukaryote. It was reported that abnormal expression of m6A-related genes is closely associated with the tumorigenesis and progression of glioma. However, the role of m6A RNA methylation in the development of glioma is still unclear. In the current study, we defined m6A-related clusters in glioma cohorts from The Cancer Genome Atlas (TCGA) database which exhibited distinct outcomes in OS. From differentially expressed genes between these clusters, m6A-associated prognostic genes were further narrowed down. Eventually, FRA10AC1, GPR85, MARCHF5, and NUAK2 were selected to form the m6Amethylation-based prognostic signature (MMS) of glioma by Cox and LASSO regression analysis. Subsequently, the efficacy and effectiveness of MMS were examined in the training, testing, and whole groups. Kaplan-Meier survival curve indicated high- and low-risk subgroups divided by MMS showed significantly different OS, and the AUCs of MMS reached 0.75 in all groups. In combined analysis with other clinical-pathological factors, MMS was proved as an independent predictive standard of glioma prognosis. In addition, gene enrichment revealed changes in signaling pathways, biological processes and hallmark gene sets between high- and low-risk subgroups. Last but not least, potential therapeutic molecules for the high-risk patient with MMS were subsequently explored. In general, our study provided MMS, a novel molecular panel closely associated with m6A methylation that holds high efficacy in predicting the prognosis of glioma.