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Identification of the Shared Gene Signatures and Pathways Between Polycystic Ovary Syndrome and Endometrial Cancer
Dan Ye1, Yi Yu2, Chengjie Xu3
1Department of Gynecology, Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai, 200433, People's Republic of China.
Aim:
Polycystic ovary syndrome (PCOS) is a common endocrine disorder with high incidence. It has been reported that patients with PCOS are at great risk of developing endometrial cancer (EC). Our study was aimed to analyze the shared gene signatures and biological mechanism between PCOS and EC.
Methods:
The datasets of PCOS and EC were downloaded from Gene Expression Omnibus (GEO) database, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network, functional enrichment analysis, miRNA and transcription factor prediction were applied to select key genes and pathways. In addition, Mendelian randomization (MR) was performed to analyze the association of PCOS with EC.
Results:
Through WGCNA and PPI network, 8 key genes namely, IL-10, CXCL8, IFNG, MMP9, PECAM1, CYBB, MYD88 and IRF4 were identified. Function enrichment analysis indicated that type I interferon signaling pathway was the most important common pathways for PCOS and EC. Furthermore, a causal effect was found between EC and PCOS (Inverse variance weighted, p < 0.05) after bidirectional MR analysis.
Conclusion:
This study, for the first time, systematically investigated the potential association between PCOS and EC through an integrative approach combining bioinformatics analysis and MR analysis. Type I interferon signaling pathway played key regulatory effect in PCOS and EC. Eight genes, such as MMP9, PECAM1 and CYBB, may be key markers linking PCOS and EC.
