Role of alternative splicing events in endometrial cancer prognosis.

Abstract

Alternative splicing (AS), as a potent and pervasive mechanism of transcriptional regulation, can expand the genome's coding capacity. Growing evidence suggests that the AS events may be associated with various types of cancer. This study aims to explore the prognostic value of AS in endometrial cancer (EC). Differently expressed AS (DEAS) events were screened by pairing the percent spliced in (PSI) value of tumor and paracancerous tissues in The Cancer Genome Atlas (TCGA) database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on their parental gene analysis of organisms. Subsequently, univariate Cox analysis was used to identify the prognostic AS events and a stepwise multi-factor Cox regression analysis was performed to further construct prognostic models. Furthermore, the diagnostic value of the prognostic model was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. Finally, the regulatory network of AS events and splicing factory in the model was also constructed. A total of 28 281 AS events were detected in EC. Of them, 42 DEAS were identified, and their parental genes were involved in tumor-related processes such as meiotic nuclear division, alpha-amino acid biosynthetic process, nuclear division, and so on. Univariate Cox analysis identified 2 289 prognostic-related AS events and constructed Cox prognostic models based on 7 different types and all types of AS events, in which the area under the curve of ROC of all types was as high as 0.882 and was better than that of 7 different splicing types. Finally, 12 splicing factors and AS events showed an obvious regulatory relationship. We use the whole genome analysis of AS events to establish a scientific prognostic prediction model for EC patients, which provides a reliable theoretical basis for the evaluation of EC clinical prognosis.