Unraveling the carcinogenic mechanisms of benzo[a]pyrene in prostate cancer: a multi-omics approach.

Although cigarette smoke is a recognized risk factor for prostate cancer (PCa), the specific contribution of benzo[a]pyrene (BaP), one of its major carcinogenic constituents, remains poorly understood. To elucidate the pathogenic mechanisms of BaP in PCa, this study integrated diverse methodologies, including network toxicology, single-cell transcriptomics, differential gene expression analysis, molecular docking, Mendelian randomization (MR), and bibliometrics. Two hundred thirty-two overlapping genes were identified between BaP targets and PCa-related genes. Hub genes TP53, EGFR, SRC, HSP90AA1, and INS were enriched in MAPK and PI3K-Akt pathways. Molecular docking confirmed strong BaP binding to these proteins. Single-cell transcriptomics revealed cell-type-specific expression patterns, while ROC (TP53 AUC = 0.67) and MR analyses (TP53 p = 2.66 × 10⁻⁶) supported their diagnostic and causal relevance. TP53 showed notable expression variability linked to Gleason scores. Bibliometric analysis highlighted TP53's evolving research significance in PCa, particularly in resistance and personalized therapy. BaP may drive PCa progression by disrupting oncogenic pathways via core targets, notably TP53, EGFR, and HSP90AA1. TP53 may act as a protective factor associated with tumor aggressiveness. These findings offer mechanistic insights into BaP-related PCa etiology and suggest potential biomarkers for diagnosis and therapy.