{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:25:25Z","timestamp":1788276325185,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may promote the initiation and progression of prostate cancer (PCa); however, its precise molecular mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>By integrating network toxicology, bioinformatics, and machine learning algorithms, potential molecular targets of PhIP in PCa were identified. Their biological significance was comprehensively evaluated through immune infiltration analysis, single-cell analysis, high-precision molecular docking, molecular dynamics simulations, and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 17 candidate genes associated with PhIP-induced PCa were identified. SHAP analysis identified SLC14A1 as the dominant contributor to model performance. Molecular docking and molecular dynamics simulations suggested that PhIP could form a stable, high-affinity complex with SLC14A1. Experimental validation showed that PhIP exposure induced cytotoxicity and was associated with decreased SLC14A1 expression, while immune infiltration and single-cell analyses further indicated its close association with the tumor immune microenvironment and epithelial localization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study offers valuable insights into the potential risks of PhIP exposure in PCa. The key genes and pathways identified may serve as potential biomarkers and therapeutic targets, providing new directions for future research and public health strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1782240","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:58:59Z","timestamp":1775800739000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["PhIP-driven prostate cancer involves key molecular regulators and immune microenvironment modulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaoan","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangbin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhe","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, The Second Hospital of Longyan","place":["Longyan, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Urology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J 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