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We systematically analyzed GEO datasets to identify BaP-related differentially expressed genes (DEBRGs). By integrating network toxicology, machine learning, molecular docking, molecular dynamics, and single-cell transcriptomics, we identified 19 significant genes, among which 7 key DEBRGs were prioritized (GSK3B, SKP2, AURKB, EPHB4, KIT, NR3C2, and CA2) in BaP-mediated BLCA. SHAP analysis highlighted GSK3B and SKP2 as important genes contributing to the predictive model. Single-cell data revealed their cell-type specific expression in the tumor microenvironment. Molecular simulations detailed interactions between BaP and target proteins. This study identified critical genes in BaP-induced bladder carcinogenesis, offering insights into underlying molecular mechanisms and potential therapeutic targets.<\/jats:p>","DOI":"10.1007\/s12672-026-05207-6","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T19:05:19Z","timestamp":1779390319000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating machine learning and structural analysis to decipher benzo[a]pyrene-induced bladder cancer networks"],"prefix":"10.1007","volume":"17","author":[{"given":"Xinzhao","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruize","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengquan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaixi","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"5207_CR1","doi-asserted-by":"crossref","unstructured":"Bukowska B, Mokra K, Micha\u0142owicz J. 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