Discovering common pathogenetic processes between polycystic ovary syndrome and uterine corpus endometrial carcinoma by bioinformatics and experimental approach

Abstract

The incidence of uterine corpus endometrial carcinoma (UCEC) is higher in individuals with polycystic ovary syndrome (PCOS) than in the general population. Nonetheless, the etiological mechanisms underlying this association remain unclear. This study aimed to delineate a shared gene signature, elucidate the pathophysiological mechanisms, and identify prospective therapeutic agents through an amalgamation of bioinformatics and in vitro studies. We identified 89 differentially expressed genes (DEGs) common to PCOS and UCEC, primarily involved in hormone signaling and immune responses. Applying the CytoHubba algorithm, we identified CCND1, CDH1, MMP9, PPP1CA, TLR2, PKM, and RPS6KA1 as key hub genes. Their expression was corroborated using a validation cohort, cellular assays, and the Human Protein Atlas (HPA) database. Notably, these hub genes demonstrated a significant positive correlation with testosterone levels in primary granulosa cells from PCOS patients. Moreover, they hold promise as diagnostic indicators of PCOS and UCEC. Immune microenvironment analysis revealed positive associations of MMP9 and TLR2 with various immune cell types and checkpoints and a spectrum of chemokines and their receptors. MAZ emerged as the pivotal transcription factor governing the expression of these hub genes in both PCOS and UCEC. Consequently, our research elucidates the common pathogenic pathways and genetic markers shared by PCOS and UCEC, providing a foundation for future therapeutic strategies and drug discovery.

Keywords

• Polycystic ovary syndrome
• Uterine corpus endometrial carcinoma
• Bioinformatics
• Gene signatures
• Immune microenvironment