Integrated gene expression analysis identifies shared inflammatory and metabolic pathways in polycystic ovarian syndrome, rheumatoid arthritis, and osteoarthritis.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects millions of women worldwide and is primarily known for its reproductive and hormonal symptoms. However, growing evidence suggests a strong link between PCOS and inflammation. Rheumatoid arthritis (RA) and osteoarthritis (OA) similarly involve systemic inflammation and immune dysregulation. Despite their distinct clinical manifestations, these disorders may share overlapping biological pathways. This study aimed to identify shared transcriptomic signatures between PCOS and autoimmune joint diseases such as RA and OA.

MATERIALS AND METHODS: RNA sequencing datasets were downloaded from the publicly available Gene Expression Omnibus (GEO) database. After processing and quality filtering, a total of 73 samples from the GSE277906 and GSE89408 datasets were selected. DEG analysis was conducted using the DE-Seq2 package in RStudio by adjusting for a significant p-value < 0.1 and |log2 fold change| > 0.5. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine functional enrichment of genes and common pathways associated with the diseases.

RESULTS: A total of 10,492 and 9,892 DEGs were identified in PCOS vs. RA and PCOS vs. OA, respectively. Key genes dysregulated among the diseases included TOMM34, DHCR24, CMAS, RBP1, and HSD3B2, and the enrichment analysis revealed overlapping pathways involving immune regulation, mitochondrial dysfunction, oxidative stress, and proteasome activity. Notably, 201 GO pathways were shared by PCOS and OA, 123 by RA and OA, and 267 by PCOS and RA. All three conditions shared a set of 57 GO pathways, including mitophagy and ER stress.

CONCLUSION: The identified common pathways signify the overlap between PCOS, RA, and OA. These findings support the hypothesis of systemic immunometabolic involvement in PCOS.