Network toxicology and bioinformatic investigation of the association between Bisphenol A and endometrial cancer

Abstract The role of Bisphenol A (BPA) in endometrial cancer (EC) remains uncertain. In this study, we integrated toxicological prediction, network toxicology, gene expression profiling, survival analysis, and molecular docking to explore potential BPA-associated molecular features in EC. Toxicological predictions from ADMETLAB 3.0 and ProTox-3 suggested a potential affinity of BPA for estrogen receptor α (ERα), along with possible involvement in oxidative stress and mitochondrial dysfunction. Integrative database analysis identified 129 putative BPA–EC–related genes, and GO/KEGG enrichment analyses indicated enrichment in angiogenesis-related processes and dysregulation of EGFR, MAPK, and FoxO signaling pathways. Analysis of TCGA-UCEC data identified 48 differentially expressed genes, among which five genes (ESR1, NOTCH1, GABARAP, B4GALT1, and PAN3) showed significant associations with overall survival in univariate Cox regression analyses. Kaplan–Meier analysis indicated that higher expression of GABARAP and NOTCH1 was associated with poorer survival, whereas higher expression of ESR1 and B4GALT1 was associated with more favorable outcomes. External validation using the GEO dataset GSE17025 supported differential expression patterns and prognostic relevance for ESR1, PAN3, B4GALT1, and NOTCH1. Molecular docking analyses indicated theoretical structural interaction feasibility between BPA and several key proteins, based on in silico simulations. Collectively, these findings provide bioinformatic and toxicogenomic evidence suggesting potential associations between BPA exposure and EC-related molecular pathways. This study is hypothesis-generating and may help prioritize candidate genes and pathways for future experimental validation and mechanistic investigation.