{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T08:57:05Z","timestamp":1781600225311,"version":"3.54.5"},"reference-count":66,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The General Project of the Joint Special Project of Local Universities in Yunnan Province","award":["202001BA070001-064"],"award-info":[{"award-number":["202001BA070001-064"]}]},{"name":"The General Project of the Joint Special Project of Local Universities in Yunnan Province","award":["202101BA070001-102"],"award-info":[{"award-number":["202101BA070001-102"]}]},{"name":"The Open Project of Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D","award":["AG2024002"],"award-info":[{"award-number":["AG2024002"]}]},{"name":"The Clinical Medicine Discipline Team Building Project of the First Affiliated Hospital of Dali University","award":["DFYYB2024026"],"award-info":[{"award-number":["DFYYB2024026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Benzo[a]pyrene (BaP) is a recognized mutagen and carcinogen, yet epidemiological links to breast cancer (BC) remain inconclusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated network toxicology, machine learning, and bioinformatics. BaP targets (ChEMBL, PharmMapper, SEA, GeneCards, OMIM) were intersected with BC genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Core regulatory genes were further screened using diverse machine-learning algorithms, and their expression levels, diagnostic performance, and associations with the tumor immune microenvironment were subsequently validated. Gene Set Variation Analysis (GSVA) was applied to assess pathway activity, and Cytoscape was used to construct a lncRNA\u2013miRNA\u2013mRNA multilevel regulatory network, thereby elucidating post-transcriptional control mechanisms. Finally, molecular docking and molecular dynamics simulations were performed to evaluate potential interactions between BaP and the core targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 216 overlapping BaP\u2013breast cancer targets were initially identified, which were significantly enriched in processes such as the mitogen-activated protein kinase (MAPK) signaling pathway. Seven core genes were identified by machine-learning\u2013based screening; among them, KIF11, INHBA, NEK2, and AURKA exhibited significantly higher expression in breast cancer tissues and were associated with worse patient prognosis and altered immune-cell infiltration. Based on pathway analyses, tumor progression was inferred to be promoted by these genes through regulation of the cell cycle, DNA replication, and cell-adhesion pathways. Molecular modeling indicated that BaP could form stable binding conformations with the proteins encoded by KIF11, AURKA, INHBA, and NEK2, suggesting possible direct interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This research provides new theoretical insights into the etiology of environmental pollutant-induced BC and offers potential molecular biomarkers for risk assessment and the formulation of targeted prevention strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.21346","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T08:40:29Z","timestamp":1781599229000},"page":"e21346","source":"Crossref","is-referenced-by-count":0,"title":["Integrative bioinformatics informed by network toxicology and machine learning elucidates the carcinogenic mechanisms of benzo[a]pyrene-induced breast cancer"],"prefix":"10.7717","volume":"14","author":[{"given":"Run","family":"Qu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Dali University, Dali, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Department of Respiratory Medicine, Dali University, Dali, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfen","family":"Ruan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Department of Gastroenterology, Dali University, Dali, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqin","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Dali Bai Autonomous Prefecture People\u2019s Hospital, Dali, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liang","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network TMDT-MaRS Centre, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University, Dali, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University, Dali, China"},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, Dali, 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