Exploring the molecular mechanism of benzo[a]pyrene affecting prostate cancer based on network toxicology and external validation.

Benzo[a]pyrene (BaP) is a polycyclic fragrant hydrocarbon contaminant commonly establish throughout the surroundings. The International Agency for Research on Cancer has classified it as a Group 1 carcinogen; however, its exact contribution to the onset of prostate cancer (PCa) is still not well defined. This study systematically explores the mechanism underlying the association between BaP exposure and prostate cancer using approaches including network toxicology, machine learning, transcriptomic validation, immune infiltration assessment, single-cell analysis, molecular docking and external validation. The results showed that BaP and prostate cancer shared 975 overlapping targets, which were predominantly enriched in signaling pathways such as PI3K-Akt. Four core genes were screened out through differential analysis and machine learning, namely CAV1, TWIST1, PRKCA, and GDF15. Transcriptome verification showed that TWIST1 and GDF15 were up-regulated, CAV1 and PRKCA were down-regulated, and the AUC of the four-gene combined diagnosis reached 0.990. Core genes are associated with cellular growth and immune cell recruitment, and single-cell sequencing verified their specific cellular distribution and immunological shifts. Molecular docking showed that BaP binds well to the core target. External validation confirmed that BaP may promotes the progression of PCa, with upregulated expression of GDF15 and downregulated expression of PRKCA in PCa. In conclusion, BaP may promote the development of PCa by regulating pathways such as CAV1, TWIST1, GDF15 and PRKCA.