Construction and Validation of an m6A RNA Methylation Regulators-Based Prognostic Signature for Esophageal Cancer

Purpose: N6-methyladenosine (m6A) is reported to play a critical role in cancer through various mechanisms. We aimed to construct and validate an m6A RNA methylation regulators-based prognostic signature for Esophageal cancer (ESCA). Materials and Methods: The RNA sequencing transcriptome data of 13 m6A RNA methylation regulators as well as clinical data were obtained from The Cancer Genome Atlas (TCGA) ESCA database. The differential expression of the regulators between ESCA tissues and normal tissues was assessed. Consensus clustering was conducted to explore the different ESCA clusters based on the expression of these regulators. LASSO Cox regression analysis was used to generate a prognostic signature based on m6A RNA methylation regulators expression. Results: Eight regulators (KIAA1429, HNRNPC, RBM15, METTL3, WTAP, YTHDF1, YTHDC1, and YTHDF2) were found to be significantly upregulated in ESCA tissues. Significant differences of survival rate and clinicopathological features were found between the two clusters. A prognostic signature, which consists of HNRNPC and ALKBH5, was constructed based on the TCGA ESCA cohort, which can serve as an independent prognostic predictor. The results of bioinformatics analysis were further successfully validated in the clinical ESCA cohort by qRT-PCR and immunohistochemistry staining. Conclusion: Our study constructed and validated an m6A RNA methylation regulatorsbased prognostic signature. This might provide important information for developing diagnostic and therapeutic strategies.