Identification of prognostic biomarkers for endometrioid endometrial carcinoma based on the miRNA and mRNA co-expression network regulated by estradiol

Abstract

Background: Endometrioid Endometrial Carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol. Methods: RNA expression profiles of EEC were obtained from The Cancer Genome Atlas database (n = 408) and the original sequencing, which was performed on endometrial cancer Ishikawa cells treated with 250 nM estradiol (n = 3), 50 nM estradiol (n = 3) or control (n = 3). The TargetScan database was used to predict the target genes of prognosis-related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs). Kaplan-Meier analysis was used to predict prognosis-related target genes to identify prognostic biomarkers and cell population landscapes, and gene expression analysis was performed to locate prognosisrelated DEGs based on single-cell transcriptomic sequencing data from the NCBI Sequence Read Archive database. Results: Four estradiol-related DEGs were associated with prognosis, and 235 overlapping target DEGs were screened and incorporated into the functional enrichment analysis and protein-protein interaction network visualization studies. Additionally, SACS and GPR157 were identified as potential biomarkers for EEC prognosis through survival analyses. Furthermore, single-cell transcriptome data were analyzed to show changes in gene expression levels in specific cell types. Conclusions: This study demonstrates that miR-142–5p–SACS and miR-30a-5p–GPR157, which are regulated by estradiol, may hold promise as diagnostic and prognostic biomarkers and novel therapeutic targets for EEC.