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Emerging evidence implicates super\u2010enhancer (SE) networks and ferroptosis dysregulation as key oncogenic drivers, though their synergistic prognostic and immune microenvironment implications are unexplored. Super\u2010enhancer\u2010related ferroptosis genes (SEFGs) were identified by intersecting SE\u2010associated and ferroptosis\u2010related genes. Using TCGA\u2010COAD (training) and GSE39582 (validation) cohorts, we established an 8\u2010gene prognostic signature via LASSO Cox regression. This signature formed the basis of a clinical nomogram with robust calibration and discrimination (C\u2010index\u00a0=\u00a00.813). High\u2010risk patients exhibited significantly reduced overall survival. Elevated risk scores correlated with advanced stage, consensus molecular subtypes (CMS1\/CMS4), high tumour mutation burden (TMB), high\u2010level microsatellite instability (MSI) and enhanced immune cell infiltration, paradoxically coupled with immunosuppressive phenotypes including increased immune checkpoint gene expression and reduced immunotherapy responsiveness, alongside increased sensitivity to SE inhibitors. JQ\u20101 RNA\u2010Seq profiling revealed three core SE\u2010driven genes, TRIB2, CAV1 and ENO3, which were significantly downregulated upon SE inhibition. Among them, TRIB2 was distinguished by its SE recurrence, tumour overexpression, prognostic value and JQ\u20101 suppression. The SEFG signature facilitates simultaneous prediction of prognosis and assessment of the immune microenvironment, providing a potential tool for colon cancer management.<\/jats:p>","DOI":"10.1049\/syb2.70043","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T20:24:01Z","timestamp":1764620641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Super\u2010Enhancer\u2010Related Ferroptosis Signature Predicts Survival and Immune Microenvironment in Colon Cancer Based on Bioinformatics Analyses and Experimental Validation"],"prefix":"10.1049","volume":"19","author":[{"given":"Luying","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Oncology Molecular Oncology Research Institute The First Affiliated Hospital of Fujian Medical University  Fuzhou China"},{"name":"Department of Oncology National Regional Medical Center Binhai Campus of the First Affiliated 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