Exploring the mechanism of bacterial lipopolysaccharide-related genes involved in polycystic ovary syndrome and its significance in diagnosis

Bacterial lipopolysaccharide (LPS), a critical component of the outer membrane of Gram-negative bacteria, activates the host immune system via pattern recognition receptors (PRRs), triggering inflammatory responses. However, the role of LPS-related genes (BLRGs) in polycystic ovary syndrome (PCOS) remains unclear. This study integrated PCOS transcriptomic and single-cell RNA sequencing (scRNA-seq) data with BLRGs from the Comparative Toxicogenomics Database (CTD). Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and consensus clustering identified candidate genes, while extreme gradient boosting (XGBoost) and random forest algorithms further screened C11orf68 and EVI5L as key biomarkers. Both genes were significantly downregulated in PCOS patients and linked to functions such as iron metabolism and heme clearance. Immune infiltration analysis revealed a significant negative correlation between activated mast cells and these biomarkers. Notably, the proportion of T cells was altered in PCOS samples, and scRNA-seq highlighted a dynamic "rising-plateau" expression pattern of C11orf68 and EVI5L during T-cell differentiation. A nomogram confirmed the predictive efficacy of these biomarkers for PCOS. Drug prediction and molecular regulatory network analysis provided insights into targeted therapies. This study is the first to uncover the regulatory role of LPS-related genes in PCOS, offering novel perspectives for early diagnosis and intervention strategies.