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In this study, an AOM\u2010DSS\u2010induced three\u2010stage colitis\u2010associated colorectal cancer (CAC) model is constructed and targeted metabolomics analysis and pathway enrichment are performed, uncovering the metabolic changes in this transition. Spatial metabolic trajectories in the \u201cnormal\u2010to\u2010normal adjacent tissue (NAT)\u2010to\u2010tumor\u201d transition, and temporal metabolic trajectories in the \u201ccolitis\u2010to\u2010dysplasia\u2010to\u2010carcinoma\u201d transition are identified through K\u2010means clustering of 74 spatially and 77 temporally differential metabolites, respectively. The findings reveal two distinct metabolic profile categories during the inflammation\u2010to\u2010cancer progression: those with consistent changes, either increasing (e.g., kynurenic acid, xanthurenic acid) or decreasing (e.g., long\u2010chain fatty acids, LCFAs), and those enriched at specific disease stages (e.g., serotonin). Further analysis of metabolites with consistent temporal trends identifies eicosapentaenoic acid (EPA) as a key metabolite, potentially exerting anti\u2010inflammatory and anti\u2010cancer effects by inhibiting insulin\u2010like growth factor binding protein 5 (IGFBP5). This study reveals novel metabolic mechanisms underlying the transition from UC to CAC and suggests potential targets to delay the progression.<\/jats:p>","DOI":"10.1002\/advs.202412551","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:22:58Z","timestamp":1737523378000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Temporal and Spatial Metabolic Shifts Revealing the Transition from Ulcerative Colitis to Colitis\u2010Associated Colorectal Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Ruiqi","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 P. R. 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