{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:30:42Z","timestamp":1786559442106,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070852"],"award-info":[{"award-number":["82070852"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270901"],"award-info":[{"award-number":["82270901"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Distant metastasis, predominantly to the liver, remains the leading cause of death in colorectal cancer (CRC), yet biomarkers that capture metastatic competence remain limited. Ferroptosis is an iron\u2010dependent, lipid peroxidation\u2010driven form of regulated cell death that can restrain tumor progression, but whether primary CRC from patients with liver metastasis shows ferroptosis\u2010resistance\u2010related features remains incompletely understood. In a small exploratory set of T\u2010stage\u2010matched primary CRC tumors with or without liver metastasis, we quantified glutathione redox and lipid peroxidation\u2010related readouts and assessed SLC7A11 and GPX4 expression. We integrated GSE62321 transcriptomic profiles with a FerrDb ferroptosis gene set, evaluated prognosis in TCGA\u2010COAD\/READ, and performed genetic knockdown, MDA assays, C11\u2010BODIPY lipid ROS staining, ferrostatin\u20101 rescue assays, and Transwell assays in CRC cell models. Primary tumors from patients with liver metastasis showed a more reduced redox profile and increased expression of core ferroptosis\u2010suppressive proteins, consistent with enhanced ferroptosis resistance potential but not direct evidence of lower in vivo ferroptotic cell death. Integrative discovery highlighted fatty acid binding protein 4 (FABP4), \u03b1\u2010synuclein (SNCA), and discoidin domain receptor 2 (DDR2) as CRC\u2010LM\u2010associated ferroptosis\u2010related candidates. High expression of each gene was associated with unfavorable disease\u2010free survival. In CRC cell models, including the lymph\u2010node\u2010metastasis\u2010derived SW620 line and additional validation lines, silencing FABP4, SNCA, or DDR2 increased bulk MDA and\/or C11\u2010BODIPY\u2010detected lipid ROS, altered ferroptosis susceptibility, and suppressed migratory and\/or invasive phenotypes. Ferrostatin\u20101 partially rescued knockdown\u2010induced viability loss, lipid ROS accumulation, and migratory\/invasive defects, supporting involvement of ferroptosis\u2010associated lipid peroxidation while not excluding broader stress\u2010response mechanisms. FABP4, SNCA, and DDR2 are CRC\u2010LM\u2010associated ferroptosis\u2010related candidates that modulate lipid peroxidation, ferroptosis susceptibility, and migratory\/invasive phenotypes in CRC cell models, warranting further validation in viability\u2010controlled and liver metastasis\u2010specific models.<\/jats:p>","DOI":"10.1002\/mc.70143","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:17:40Z","timestamp":1782850660000},"page":"1063-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Colorectal Cancer Liver Metastasis\u2010Associated Ferroptosis\u2010Related Genes Modulate Lipid Peroxidation in Colorectal Cancer Cells"],"prefix":"10.1002","volume":"65","author":[{"given":"Zheng","family":"Ge","sequence":"first","affiliation":[{"name":"Department of General Surgery Qilu Hospital of Shandong University Jinan 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