{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:16:19Z","timestamp":1783419379790,"version":"3.54.6"},"reference-count":81,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Iron is essential for normal cellular function, but its dysregulation is increasingly recognized as a key factor in colorectal tumorigenesis. This review provides an integrated overview of iron-related biomarkers across the full spectrum of colorectal neoplasia, from preneoplastic lesions to advanced colorectal cancer (CRC). Evidence suggests that alterations in iron metabolism begin early, at the level of colorectal adenomas, where increased iron uptake and impaired export contribute to local iron accumulation and oxidative stress. As lesions progress to carcinoma, this imbalance becomes more pronounced, leading to expansion of the intracellular labile iron pool and supporting tumor growth, metabolic adaptation, and genomic instability. At the systemic level, patients often exhibit reduced circulating iron despite preserved or elevated ferritin levels, reflecting inflammation-driven functional iron deficiency. This pattern is largely mediated by dysregulation of the hepcidin\u2013ferroportin axis. In this context, transferrin saturation and soluble transferrin receptor may provide a more accurate assessment of iron availability than ferritin alone. At the tissue level, increased expression of iron import proteins and impaired iron export promote intracellular iron retention. Excess iron further contributes to reactive oxygen species generation, leading to damage of DNA, lipids, and proteins. Clinically, iron-related biomarkers show variable diagnostic performance but may offer prognostic value. Integrating systemic and tissue biomarkers could improve risk stratification and support personalized approaches across the CRC continuum.<\/jats:p>","DOI":"10.3390\/diagnostics16132081","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:48:32Z","timestamp":1782992912000},"page":"2081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iron Metabolism in the Colorectal Tumor Microenvironment: Current Evidence and Clinical Implications"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1926-6456","authenticated-orcid":false,"given":"Anamaria-Vl\u0103du\u021ba","family":"Tomoiag\u0103","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, 4th Medical Discipline, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-2291","authenticated-orcid":false,"given":"Angela","family":"Cozma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 4th Medical Discipline, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4090-0164","authenticated-orcid":false,"given":"Cezara-Andreea","family":"Gerdanovics","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 4th Medical Discipline, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5185-9512","authenticated-orcid":false,"given":"Alexandru","family":"Gerdanovics","sequence":"additional","affiliation":[{"name":"Neurology Department, Clinical Rehabilitation Hospital, Viilor Street, No. 46-50, 400066 Cluj-Napoca, Romania"},{"name":"Neuroscience Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5087-9282","authenticated-orcid":false,"given":"Mircea-Vasile","family":"Milaciu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 4th Medical Discipline, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoleta-Valentina","family":"Leach","sequence":"additional","affiliation":[{"name":"Department 2, Faculty of Nursing and Health Sciences, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasile","family":"Negrean","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 4th Medical Discipline, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0218oimi\u021ba-Mihaela","family":"Suciu","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 1-3 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0803","authenticated-orcid":false,"given":"Simona Valeria","family":"Clichici","sequence":"additional","affiliation":[{"name":"Department of Physiology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 1-3 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4435-142X","authenticated-orcid":false,"given":"Olga Hilda","family":"Or\u0103\u0219an","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, 4th Medical Discipline, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Republicii Street, No. 18, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1098501","DOI":"10.3389\/fonc.2023.1098501","article-title":"Iron Metabolism in Colorectal Cancer","volume":"1","author":"Huang","year":"2023","journal-title":"Front. 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