Identification of Five m6A-Related lncRNA Genes as Prognostic Markers for Endometrial Cancer Based on TCGA Database.

Abstract

Background Due to difficulties involved in its early diagnosis and adequate prognostication, uterine corpus endometrial carcinoma (UCEC) is one of the most serious threats to human health, with the five-year survival rate being as low as roughly 60%. The discovery of specific biomarkers that serve as prognosticators of UCEC is of great significance. The role of N6-methyladenosine- (m6A-) related long noncoding RNAs (lncRNAs) in the pathogenesis of UCEC remains undefined. In this study, we explored the expression profiles of m6A-related lncRNAs of patients with UCEC and identified novel prognostic markers for UCEC. Methods Gene expression and clinical data were extracted from The Cancer Genome Atlas. Coexpression analysis was performed to identify m6A-related lncRNAs, which were entered into univariate Cox regression models for evaluating the prognosis of UCEC. Clusters of UCEC patients and enrichment pathways were identified using consistent data clustering and gene set enrichment analysis (GSEA). A risk score model was established, and Kaplan–Meier analysis was conducted for investigating overall survival (OS) across two patient groups (high risk and low risk). Lastly, the relationship between the risk score and the cell content of 22 types of immune cells, clusters, age, programmed cell death 1 ligand-1 (PD-L1) expression level, immune score, and pathological grade was analyzed. Results We identified a total of 2084 lncRNAs associated with m6A, of which 32 lncRNAs were prognostically relevant. Two clusters (clusters 1 and 2) of patients with UCEC were defined; patients in cluster 1 were found to have significantly higher pathological grades and shorter overall survival time compared to those in cluster 2. GSEA showed that “MITOTIC SPINDLE and other pathways” were more enriched in cluster 1. Five major lncRNAs associated with m6A were screened out, and risk score modeling was used for UCEC prognosis prediction. High risk scores were associated with a shorter OS. The risk score was also verified as an independent prognostic indicator for UCEC and was related to immune cell infiltration levels. Finally, we observed a higher pathological grade and greater levels of PD-L1 in the high-risk group than in the low-risk group of patients. Conclusions m6A-related lncRNAs play an important role in UCEC progression. The risk-based model constructed from the five key m6A-related lncRNAs was implicated in immune cell infiltration and can potentially be an accurate prognosticator for UCEC.