Screening and identification of MSX1 for predicting progestin resistance in endometrial cancer

Abstract

Background Progestin resistance is a critical obstacle for endometrial conservative therapy. Therefore, the studies to acquire a more comprehensive understanding of the mechanisms are very important. However, the pivotal roles of essential molecules are still unexplored.Methods We downloaded GSE121367 from the GEO database. The “limma” R language package was applied to identify differentially expressed genes (DEGs). We conducted Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) analysis. Protein–protein interaction was constructed by STRING and visualized in Cytoscape. The tumor immune microenvironment was explored by TISIDB database. Methylation validation and overall survival analysis was conducted by TCGA database. In addition, the upstream modulators of hub genes were predicted by miRTarBase and Network Analyst database.Results A total of 3282 DEGs were identified and they were mostly enriched in cell adhesion pathway. We screened out ten hub genes including CDH1, JAG1, PTGES, EPCAM, CNTNAP2, TBX1, MSX1, KRT19, OAS1 and DAB2 among different groups, whose genomic alteration rates were low based on the current endometrial carcinoma sample sets. Has-miR-335-5p, has-miR-124-3p, MAZ and TFDP1 were the most prominent upstream regulators. The methylation status of CDH1, JAG1, EPCAM and MSX1 were decreased, corresponding to their high protein expression, which also predicted better overall survival. The homeobox protein of MSX1 showed significantly tissue specificity and better prognostic value.Conclusions Our study identified the gene of MSX1 promised to be the specific indicator. This would shed new light on the underlying biological mechanism to overcome progestin resistance of endometrial cancer.