Profiling the m6A-regulated RNA expression patterns and alternative splicing features in esophageal carcinoma

Abstract The mRNA post-modifications, such as N 6 -methyladenosine (m 6 A) modification, have been found to play a role in a variety of cancers. The impact of m 6 A modification in esophageal cancer (EC), which is one of the most frequently occurred malignancies worldwide, is still unclear. Here we evaluated the m 6 A modification patterns in 161 EC samples based on 22 kinds of m 6 A regulatory factors. We constructed the m 6 Ascore, in which the principal component analysis (PCA) was used to quantify the m 6 A modification pattern of a single tumor. Two distinct m 6 A modification patterns were determined, namely risky pattern and favorable pattern. Patients of favorable pattern positively correlated with the prognosis, whereas patients of risky pattern had a negative correlation. Furthermore, the differentially expressed genes that closely relate to the prognosis of EC patients were screened and clustered, yielding a principal component analysis coefficient to indicate the m 6 Ascore. Resultantly, the prognosis of EC patients is highly correlated with the combined effects of m 6 Ascore, stage and TMB. In addition, the correlation analysis revealed that the key transcription factor YY1 determines the m 6 Ascore via regulating the gene expression. The mutil-Cox analysis constructed the risk prediction model of alternative splicing, which negatively correlated with the m 6 Ascore. Moreover, the m 6 A demethylase ALKBH5 was found to have a most significant negative correlation with the risk score, and might regulate the alternative splicing of ABI1-ES. Altogether, we established a set of scoring system to quantify the m 6 A modification pattern with RNA alternative splicing events in individual EC patients.