Comprehensive analysis of the molecular dynamics of bisphenol compounds and prediction of their effects on prostate cancer progression.

Bisphenols are a class of widely occurring environmental endocrine disruptors, but a comprehensive understanding of their systemic effects on prostate cancer progression under conditions of low-concentration exposure remains lacking. This study established a comprehensive research framework integrating bioinformatics analysis, functional experiments, and structural biology analysis to systematically evaluate the cancer-promoting effects of eight bisphenol compounds, namely, BPA, BPAF, BPB, BPC, BPE, BPF, BPS, and BPZ, in prostate cancer. Enrichment analysis revealed that, across cancer types, most bisphenol-related features ranked prostate cancer among the top 10 most affected cancers, suggesting a strong association with prostate cancer. Functional experiments further demonstrated that exposure to low concentrations of bisphenol significantly promotes the proliferation of prostate cancer cells. Prognostic analysis revealed that patients in the high-score group for each bisphenol were associated with a significantly shorter progression-free interval (PFI). Subsequently, we constructed a total bisphenol score model that was associated with tumor progression in patients. Molecular docking and molecular dynamics analyses indicated that all eight bisphenols can form relatively stable complexes with the androgen receptor (AR). In summary, this study demonstrates that exposure to low concentrations of bisphenols may promote the malignant progression of prostate cancer through interactions with central molecules in the AR pathway, providing a systematic basis for understanding the class-specific effects of bisphenols in prostate cancer and their potential value in risk stratification and mechanistic research.