Novel Insights into the Pathogenic Role of CSF1R in Endometriosis

Endometriosis (EM) is a prevalent gynecological disorder linked to pelvic pain, menstrual disturbances, and infertility. Despite its clinical burden, the molecular mechanisms underlying EM remain elusive, necessitating the discovery of novel biomarkers and therapeutic targets. This study explored the role of colony-stimulating factor 1 receptor (CSF1R) in EM through an integrative approach combining bioinformatics and experimental validation. Differentially expressed genes (DEGs) were identified from the GSE11691 dataset using the limma package. Weighted Gene Co-expression Network Analysis (WGCNA) identified disease-associated gene modules. A Protein-Protein Interaction (PPI) network was constructed, and candidate genes were selected using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest algorithms. Expression and function of CSF1R were validated in hEM15A cells via RT-qPCR, Western blotting, CCK-8, EdU, wound healing, and Transwell assays. WGCNA and PPI network analysis revealed a significant enrichment of genes within the PI3K/AKT/mTOR signaling pathway. Cross-validation using LASSO and Random Forest identified THBS2, CSF1R, IL-4R, and FLT1 as potential biomarkers. Among them, CSF1R was found to be significantly overexpressed in endometriotic stromal cells. Knockdown of CSF1R markedly suppressed cell proliferation, migration, and invasion, accompanied by decreased p-AKT expression. Rescue experiments using an AKT activator partially reversed these effects, supporting the functional role of CSF1R in modulating the AKT signaling pathway. CSF1R promotes the progression of endometriosis by modulating AKT signaling. It may serve as a valuable diagnostic biomarker and therapeutic target, providing new insights into endometriosis pathogenesis and treatment strategies.