The identification of key genes and pathways in polycystic ovary syndrome by bioinformatics analysis of next-generation sequencing data

Abstract Background Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder. The specific molecular mechanism of PCOS remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of PCOS. Methods The next-generation sequencing (NGS) dataset GSE199225 was downloaded from the gene expression omnibus (GEO) database and NGS dataset analyzed is obtained from in vitro culture of PCOS patients’ muscle cells and muscle cells of healthy lean control women. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the gene ontology (GO) and REACTOME pathways of the differentially expressed genes. A protein–protein interaction (PPI) network was constructed and module analysis was performed using HiPPIE and cytoscape. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed. The hub genes were validated by using receiver operating characteristic (ROC) curve analysis. Results We have identified 957 DEG in total, including 478 upregulated genes and 479 downregulated gene. GO terms and REACTOME pathways illustrated that DEG were significantly enriched in regulation of molecular function, developmental process, interferon signaling and platelet activation, signaling, and aggregation. The top 5 upregulated hub genes including HSPA5, PLK1, RIN3, DBN1, and CCDC85B and top 5 downregulated hub genes including DISC1, AR, MTUS2, LYN, and TCF4 might be associated with PCOS. The hub gens of HSPA5 and KMT2A, together with corresponding predicted miRNAs (e.g., hsa-mir-34b-5p and hsa-mir-378a-5p), and HSPA5 and TCF4 together with corresponding predicted TF (e.g., RCOR3 and TEAD4) were found to be significantly correlated with PCOS. Conclusions These study uses of bioinformatics analysis of NGS data to obtain hub genes and key signaling pathways related to PCOS and its associated complications. Also provides novel ideas for finding biomarkers and treatment methods for PCOS and its associated complications.