{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:03:54Z","timestamp":1784696634326,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bisphenol A (BPA) is a potential risk factor for pancreatic ductal adenocarcinoma (PDAC). This study integrated network toxicology, molecular docking, molecular dynamics (MD) simulations, and TCGA clinical data analysis to explore the potential molecular mechanisms linking BPA exposure to PDAC risk. BPA\u2013PDAC intersection targets were identified through multi-database screening, followed by protein\u2013protein interaction (PPI) network construction to screen core hub genes. A total of 10 core hub genes were identified via PPI analysis combined with the Maximal Clique Centrality (MCC) algorithm. Molecular docking demonstrated that ESR1 exhibited one of the strongest binding affinities for BPA (\u22128.2 kcal\/mol), and MD simulations confirmed favorable thermodynamic stability of the BPA\u2013ESR1 complex. TCGA analysis revealed stage-dependent expression patterns: early stages showed downregulation of TP53 and BCL2, whereas advanced stages showed upregulation of BCL2L1, HSP90AA1, and HSP90AB1, while ESR1, HIF1A, and PARP1 remained consistently low. These findings suggest that BPA may promote PDAC progression by disrupting ER\u03b1-mediated endocrine signaling and impairing DNA repair through PARP1 interference, providing candidate molecular targets and a hypothesis-generating foundation for pancreatic cancer risk assessment, warranting further experimental validation.<\/jats:p>","DOI":"10.3390\/ijms27146439","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"6439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Network Toxicology with Molecular Dynamics Simulations to Reveal Key Targets and Binding Mechanisms of Bisphenol A in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2105-323X","authenticated-orcid":false,"given":"Xueru","family":"Li","sequence":"first","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Interface Process and Soil Health, College of Resources and Environment, Southwest University, Chongqing 400716, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"An","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University, Yining 835000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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