Employing network toxicology, molecular docking, machine learning, and single-cell analysis to analyze BPA exposure-induced ccRCC.

This study investigates the molecular mechanisms underlying bisphenol A (BPA)-induced clear cell renal cell carcinoma (ccRCC). We integrated transcriptomic data from multiple GEO datasets and performed differential expression analysis and WGCNA to identify BPA-associated candidate genes. Enrichment analyses implicated pathways including cell adhesion, lipid metabolism, arachidonic acid signaling, and innate immune response. Using twelve machine learning algorithms, we identified four core genes (ITGB2, TBXAS1, LIPA, and CLEC7A), all upregulated in ccRCC. Molecular docking suggested stable BPA-protein interactions with favorable binding energies. Single-cell analysis showed predominant expression of these genes in monocytes and macrophages. LIPA was elevated in kidney cancer tissues and associated with clinical outcomes. In vitro experiments confirmed that BPA exposure promoted ccRCC cell progression by regulating core gene expression. This integrated approach offers new insights into the molecular mechanisms of BPA-induced ccRCC and identifies potential biomarkers for environmental risk assessment.