Identification of a m6A RNA methylation regulators-based signature for predicting the prognosis of esophageal adenocarcinoma

Abstract

BackgroundN6-methyladenosine (m6A) is an abundant modification in RNAs that affects RNA metabolism, and it is reported to be closely related to cancer occurrence and metastasis. The aim of this study was to identify novel prognostic biomarkers by using m6A RNA methylation regulators capable of improving the risk-stratification criteria of survival for esophageal adenocarcinoma patients.MethodsThe gene expression data of 16 m6A methylation regulators and its relevant clinical information were extracted from The Cancer Genome Atlas (TCGA) database. The expression pattern of these m6A methylation regulators was evaluated. Consensus clustering analysis was conducted to identify clusters of esophageal adenocarcinoma patients with different prognosis. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were performed to construct multiple-gene risk signature. A survival analysis was carried out to determine the prognosis significance.ResultsTen m6A methylation regulators (HNRNPA2B1, HNRNPC, YTHDF1, METTL3, YTHDF2, RBM15, YTHDC1, WTAP, KIAA1429 and YTHDF3) showed significant up-regulation in tumor tissue. Consensus clustering analysis identified three clusters of esophageal adenocarcinoma patients with different overall survival. A five-gene signature, HNRNPA2B1, KIAA1429, WTAP, METTL16 and ALKBH5, was constructed to serve as a prognostic indicator for distinguish esophageal adenocarcinoma patients with different prognosis. The receiver operator characteristic (ROC) curve which indicated the area under the curve (AUC) were 0.803, demonstrated that the prognostic signature had preferable prediction efficiency.Conclusionsm6A methylation regulators exert as potential biomarkers for prognostic stratification of esophageal adenocarcinoma patients and might help clinicians make individualized therapy for this patient population.