Abstract
BACKGROUND: Esophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA. METHODS: RNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: In ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.