{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T23:44:25Z","timestamp":1782517465062,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Stemness has been proposed as a unifying driver of invasion, treatment resistance, and relapse in oral squamous cell carcinoma (OSCC). We synthesized two complementary evidence streams to determine whether higher stemness predicts poorer survival in OSCC: (i) computational stemness signatures derived from transcriptomic\/epigenetic data and (ii) tissue cancer stem cell (CSC) immunophenotypes by immunohistochemistry (IHC). Methods: Following PRISMA 2020, we searched PubMed\/MEDLINE, Embase, Scopus, and SciELO. Adults with histologically confirmed OSCC were eligible. Primary outcome was overall survival (OS); disease-specific survival (DSS) and recurrence-free survival (RFS) were secondary. Two parallel meta-analyses pooled effects within domains; random-effects restricted maximum likelihood (REML) models were applied. Results: Of 785 records, 11 studies met criteria. For computational signatures (k = 6), higher stemness was associated with poorer OS (pooled HR 2.24, 95% CI 1.61\u20133.12; I2 \u2248 49%). Sensitivity excluding the single unadjusted Kaplan\u2013Meier (KM)-derived estimate yielded a similar effect (HR 2.13, 95% CI 1.56\u20132.89). For CSC-IHC (main analysis, k = 2), CSC-positive profiles predicted worse OS (pooled HR 2.01, 95% CI 1.42\u20132.84; I2 \u2248 0%); results were robust to excluding an internally inconsistent study (single-study HR 2.078). An exploratory sensitivity analysis, including a 1-year HR (different time horizon), increased heterogeneity and was not considered definitive. A functional meta-synthesis converged on epithelial\u2013mesenchymal transition\/extracellular matrix remodeling, hypoxia\/glycolysis, redox\/ferroptosis resistance, and ribosome\/rRNA biogenesis, supporting biological plausibility across modalities. Conclusions: Across computational and IHC evidence, stemness consistently portends inferior OS in OSCC, offering a biologically anchored framework for risk stratification and testable therapeutic hypotheses.<\/jats:p>","DOI":"10.3390\/medsci14010021","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:08:00Z","timestamp":1767197280000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Computational Stemness and Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma: A Systematic Review, Dual Meta-Analysis, and Functional Meta-Synthesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-1416","authenticated-orcid":false,"given":"Carlos M.","family":"Ardila","sequence":"first","affiliation":[{"name":"Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India"},{"name":"Biomedical Stomatology Research Group, Basic Sciences Department, Faculty of Dentistry, Universidad de Antioquia U de A, Medell\u00edn 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-7489","authenticated-orcid":false,"given":"Eliana","family":"Pineda-V\u00e9lez","sequence":"additional","affiliation":[{"name":"Biomedical Stomatology Research Group, Basic Sciences Department, Faculty of Dentistry, Universidad de Antioquia U de A, Medell\u00edn 050010, Colombia"},{"name":"Faculty of Dentistry, Instituci\u00f3n Universitaria Visi\u00f3n de las Am\u00e9ricas, Medell\u00edn 050040, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8631-4910","authenticated-orcid":false,"given":"Anny M.","family":"Vivares-Builes","sequence":"additional","affiliation":[{"name":"Biomedical Stomatology Research Group, Basic Sciences Department, Faculty of Dentistry, Universidad de Antioquia U de A, Medell\u00edn 050010, Colombia"},{"name":"Faculty of Dentistry, Instituci\u00f3n Universitaria Visi\u00f3n de las Am\u00e9ricas, Medell\u00edn 050040, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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