{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:48:27Z","timestamp":1791679707957,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: S100A11, a calcium-binding S100 family protein, is increasingly implicated in carcinogenesis, yet its molecular regulation and clinical relevance across cancers remain unclear. Hepatocellular carcinoma (HCC) carries a dismal prognosis, in part due to a lack of reliable biomarkers for risk stratification of established disease. Methods: We conducted a pan-cancer analysis of S100A11 genomic alterations across 31 studies (10,767 samples) obtained from TCGA, encompassing copy number alterations, somatic mutations, and DNA methylation. HCC-specific analyses evaluated S100A11 expression, its potential as a diagnostic\/prognostic marker, co-expression networks, and pathway enrichment using TCGA-LIHC data, with univariate and multivariate Cox regression to assess survival associations. Results: S100A11 alterations were predominantly driven by copy number amplification, with the highest frequencies in hepatobiliary cancers, lung and breast cancers. Copy number amplification showed a consistent inverse relationship with promoter methylation, indicating amplification-driven transcriptional activation. In HCC, S100A11 was markedly overexpressed compared with normal liver tissue, with strong diagnostic discriminatory capacity. High S100A11 expression was significantly associated with inferior overall survival (log-rank p = 0.032; HR = 1.46, 95% CI 1.03\u20132.06) and remained an independent predictor of overall survival after adjustment for age, sex, and AJCC pathologic stage (HR = 1.27, 95% CI 1.01\u20131.60, p = 0.038). Co-expression and pathway analyses demonstrated an association between S100A11 and metabolic reprogramming, extracellular matrix remodelling, and immune dysregulation. Conclusions: These findings identify S100A11 as a candidate diagnostic and prognostic biomarker in HCC whose overexpression is associated with metabolic reprogramming, ECM remodelling, and immune dysregulation, warranting experimental validation of a mechanistic role.<\/jats:p>","DOI":"10.3390\/cancers18172848","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amplification-Driven S100A11 Overexpression in Hepatocellular Carcinoma Is Associated with Metabolic Reprogramming, ECM Remodelling, and Immune Evasion: A Pan-Cancer Genomic Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-6059","authenticated-orcid":false,"given":"Stuart","family":"Lutimba","sequence":"first","affiliation":[{"name":"Cancer, Infection and Therapeutics Research Group, School of Allied Health and Life Sciences, College of Health and Life Sciences, London South Bank University, 103 Borough Road, London SE1 0AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9215-8213","authenticated-orcid":false,"given":"Eiman","family":"Aleem","sequence":"additional","affiliation":[{"name":"Cancer, Infection and Therapeutics Research Group, School of Allied Health and Life Sciences, College of Health and Life Sciences, London South Bank University, 103 Borough Road, London SE1 0AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nrc3893","article-title":"S100 proteins in cancer","volume":"15","author":"Bresnick","year":"2015","journal-title":"Nat. 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