{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:32:30Z","timestamp":1785407550679,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Provincial Natural Science fund subject of China","award":["2024L3014"],"award-info":[{"award-number":["2024L3014"]}]},{"name":"Fujian Provincial Natural Science fund subject of China","award":["2025J01935"],"award-info":[{"award-number":["2025J01935"]}]},{"name":"Fujian Provincial Natural Science fund subject of China","award":["2022J01361"],"award-info":[{"award-number":["2022J01361"]}]},{"DOI":"10.13039\/501100008021","name":"Fujian University of Traditional Chinese Medicine","doi-asserted-by":"crossref","award":["XJC2023004"],"award-info":[{"award-number":["XJC2023004"]}],"id":[{"id":"10.13039\/501100008021","id-type":"DOI","asserted-by":"crossref"}]},{"award":["XJC2023004"],"award-info":[{"award-number":["XJC2023004"]}],"id":[{"id":"https:\/\/ror.org\/05n0qbd70","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation Project of China","doi-asserted-by":"crossref","award":["82574921"],"award-info":[{"award-number":["82574921"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Benzo[a]pyrene (BaP), a common food contaminant, is a recognized gastric carcinogen. This study aimed to identify therapeutic targets and repurposed drugs for gastric cancer (GC) using BaP as a network toxicology query. Methods: An integrated strategy combining network toxicology, multi-omics, machine learning (Random Forest, LASSO, SVM-RFE), and experimental validation was applied. Results: By intersecting GC-associated genes with BaP-related targets and machine learning, we identified three hub genes. The logistic regression model further revealed KCNE2 as a protective factor (OR = 0.515, 95% CI: 0.383\u20130.692), while SULF1 (OR = 2.940, 95% CI: 1.399\u20136.179) and TIMP1 (OR = 5.351, 95% CI: 2.020\u201316.743) were identified as potential risk factors. Survival analysis confirmed their prognostic significance. Single-cell transcriptomics descriptively showed TIMP1 and SULF1 enrichment in malignant\/stromal cells and fibroblasts, respectively, whereas KCNE2 was restricted to normal epithelial cells and silenced in tumors. GSVA implicated epigenetic regulation, ECM remodeling, and TGF-\u03b2 signaling. Molecular docking and dynamics simulations suggested that BaP can form stable complexes with DNMT1 and DNMT3A. Accordingly, drug enrichment analysis identified DNMT inhibitor 5-azacytidine as a top candidate. Cellular experiments confirmed that 5-azacytidine selectively inhibited GC cells and was associated with modulation of the DNMT3A\u2013KCNE2 axis. Conclusions: Our findings provide a novel molecular target and a repurposed drug for GC from the perspective of a food contaminant.<\/jats:p>","DOI":"10.3390\/ph19071060","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:51Z","timestamp":1783606671000},"page":"1060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Food Contaminant to Therapeutic Target: Identification of KCNE2 and 5-Azacytidine for Gastric Cancer via Multi-Omics, Machine Learning, and In Vitro Validation"],"prefix":"10.3390","volume":"19","author":[{"given":"Meimei","family":"Chen","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"Fujian Key Laboratory of TCM Health Status Identification, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Physics and Information Engineering, Fuzhou University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjian","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"Fujian Key Laboratory of TCM Health Status Identification, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"Fujian Key Laboratory of TCM Health Status Identification, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruina","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"Fujian Key Laboratory of TCM Health Status Identification, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"Fujian Key Laboratory of TCM Health Status Identification, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Gan","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"Fujian Key Laboratory of TCM Health Status Identification, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bukowska, B., and Sici\u0144ska, P. 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