Exploring the potential role of ENPP2 in polycystic ovary syndrome and endometrial cancer through bioinformatic analysis.

BACKGROUND

Growing evidence indicates a significant correlation between polycystic ovary syndrome (PCOS) and endometrial carcinoma (EC); nevertheless, the fundamental molecular mechanisms involved continue to be unclear.

METHODS

Initially, differential analysis, the least absolute shrinkage and selection operator (LASSO) regression, and support vector machine-recursive feature elimination (SVM-RFE) algorithms were employed to identify candidate genes associated with ferroptosis in PCOS. Subsequently, the TCGA-UCEC data were utilized to pinpoint the core gene. Then, the expression of in granulosa cells and endometrium of PCOS was validated using real-time PCR (RT-qPCR). Additionally, we investigated the role of in the progression from PCOS to EC through western blotting (WB), colony formation assay, cell scratch assay, transwell assay, and immunofluorescence (IF). Subsequently, gene set enrichment analysis (GSEA) analyses were conducted to identify common pathways involved in PCOS and EC, which were then verified by RT-qPCR. Finally, immune infiltration and the tumor microenvironment (TME) were explored to examine the involvement of in EC progression.

RESULTS

The datasets TCGA-UCEC (pertaining to EC), GSE34526, GSE137684, and GSE6798 (related to PCOS) were procured and subjected to analysis. The gene has been recognized as the shared element connecting PCOS and EC. Next, we observed a significant downregulation of expression in the granulosa cells in PCOS compared to the normal patients, while an upregulation of expression was observed in the endometrium of hyperandrogenic PCOS patients relative to the normal. , the WB revealed that 5-dihydrotestosterone (DHT) upregulated expression in Ishikawa and HEC-1-A cells. Additionally, we found that promoted the proliferation, migration, and invasion of Ishikawa and HEC-1-A cells. Subsequently, we discovered that overexpressed may lead to an increase in (aromatase) and mRNA level. IF demonstrated that increased the expression of , suggesting a regulatory role for in hormonal response within PCOS and EC. Our findings indicated a significant correlation between expression and the modulation of immune responses.