Identification of Five m6A-Relevant mRNAs Signature and Risk Score for The Prognostication of Gastric Cancer

Introduction: N6-methyladenosine (m6A) is the most abundant form of methylation modification in eukaryotic cell mRNA. However, the role of m6A in gastric cancer is unclear, which is one of the most common gastrointestinal malignancies. The m6A-relevant mRNA signatures and risk scores are determined to predict the prognosis of gastric cancer in this study. Methods: : The expression profiles and clinical information of 367 patients were downloaded from the Cancer Genome. Cluster analysis and univariate Cox analysis were used to identify the regulatory factors of RNA methylation associated with gastric cancer prognosis. The co-expression network was constructed by the WGCNA package in R. Then, the correlations between module eigengenes and clinical traits were calculated to identify the relevant modules. We used univariate Cox analysis to screen for genes that were significantly associated with prognosis in the module (P < 0.01 was considered significant). We identified hub genes by LASSO and multivariate analysis, and developed a Cox prognostic model. Finally, the hub gene expression values weighted by the coefficients from the LASSO regression generated a risk score for each patient, receiver operating characteristic (ROC) and Kaplan-Meier curves were used to assess the prognostic capacity of the risk scores. Results: : HNRNPC was shown as P1 in the TCGA gastric cancer data set, which might be a pathogenic factor affecting the prognosis of gastric cancer. The results indicated that AARD, ASPN, SLAMF9, MIR3117 and DUSP1 were hub genes affecting the prognosis of gastric cancer patients, and the m6A methylation of these mRNAs might be regulated by HNRNPC. The risk score = − (0.166195281×AARD + 0.016850602×ASPN + 0.591607997×SLAMF9 + 0.591607997×MIR3117 + 0.00276337×DUSP1), and our results indicated a bad performance of the five-gene signature for survival prediction (P < 0.05). Conclusion: HNRNPC (a m6A RNA methylation regulator) can participate in the serious progression of gastric cancer by regulating the m6A of AARD, ASPN, SLAMF9, MIR3117 and DUSP1, which may be used for prognosis stratification and treatment strategy formulation.