Integrated Genomic Analysis Reveals New Diagnostic Biomarkers and Immune Mechanisms for Polycystic Ovary Syndrome

Ning Huang,1 LuYun Lou2 1Cixi Integrated Traditional Chinese and Western Medicine Healthcare Group, Ningbo, Zhejiang, 315300, People’s Republic of China; 2Henghe Central Health Center of Cixi City, Ningbo, Zhejiang, 315300, People’s Republic of ChinaCorrespondence: Ning Huang, Email [email protected] LuYun Lou, Email [email protected]: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with metabolic dysregulation and chronic inflammation. This study employed bioinformatics approaches to analyze the roles of neutrophil extracellular traps (NETs)-related genes (NETRGs) and mitochondria-related genes (MRGs) in PCOS pathogenesis.Methods: Through differential expression analysis, enrichment studies, and machine learning models, we identified 18 differentially expressed neutrophil extracellular trap- and mitophagy-related genes (NETMRDEGs), such as S100A9, MYH9, and ATG5. Functional enrichment revealed their involvement in IL-17 signaling and neutrophil chemotaxis. A LASSO regression model incorporating these genes demonstrated high diagnostic accuracy (AUC > 0.9). Immune infiltration analysis highlighted activated B cells and effector memory CD8+ T cells as key contributors. Moreover, protein-protein interaction (PPI) networks further elucidated functional synergies among NETMRDEGs.Results: The study identified distinct molecular clusters in PCOS patients based on the expression of NETMRDEGs. Cluster 2 exhibited higher immune infiltration (eg, gamma delta T cells and eosinophils) and severe metabolic dysfunction. The LASSO model achieved superior diagnostic performance (AUC: 0.93) compared to traditional biomarkers such as testosterone (AUC: 0.68). Experimental validation in a PCOS mouse model confirmed elevated expression of hub genes (S100A9, MYH9, and ATG5) and increased granulosa cell apoptosis.Conclusion: The interaction between NETRGs and MRGs forms a “dual-engine” mechanism driving PCOS pathogenesis. This study proposed a novel diagnostic model and therapeutic targets (eg, DNase I and urolithin A), advancing precision medicine for PCOS.Keywords: polycystic ovary syndrome, neutrophil extracellular traps, mitochondria-related genes, immune infiltration, diagnostic model