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Galectins (Gal) have been the subject of intensive research, but the comparative prognostic value of each Gal type is not yet understood. Therefore, a literature search for evaluating galectins as prognostic biomarkers in HNSCC was conducted. The relationship between Gal expression in HNSCC with HPV and TP53 mutational status was assessed using the UALCAN database. The impact of these biomarkers on prognosis was analyzed using ToPP and CPPA web tools. The expression of galectins in the tumor microenvironment and the impact on prognosis depending on the cancer immune subtype were analyzed using single-cell RNA sequencing. Gal-1 and Gal-3BP were shown to be promising biomarkers with a triple function for the prediction of HPV and TP53 mutational status, stratification of the HNSCC prognosis, and prediction of the response to treatment. In addition, these two galectins have been shown to be most influenced by the tumor microenvironment of HNSCC. Gal-1 and Gal-3BP are the most promising galectins in HNSCC. Furthermore, this study highlights the need for further studies to evaluate galectins in HNSCC and clarify the role of individual Gals in the patient\u2019s stratification.<\/jats:p>","DOI":"10.3390\/biomedicines12030529","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T03:35:48Z","timestamp":1709004948000},"page":"529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0014-2282","authenticated-orcid":false,"given":"Oriana","family":"Barros","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Surgical Department of Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto. CCC), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3379-2254","authenticated-orcid":false,"given":"Vito Giuseppe","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, Italy"}]},{"given":"Lucio","family":"Santos","sequence":"additional","affiliation":[{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Surgical Department of Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto. CCC), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-4051","authenticated-orcid":false,"given":"Rita","family":"Ferreira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-5805","authenticated-orcid":false,"given":"Rui","family":"Vitorino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Institute of Biomedicine iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Surgical Department of Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto. CCC), 4200-072 Porto, Portugal"},{"name":"UnIC, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.annonc.2020.07.011","article-title":"Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Machiels","year":"2020","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"873","DOI":"10.6004\/jnccn.2020.0031","article-title":"Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology","volume":"18","author":"Pfister","year":"2020","journal-title":"J. Natl. Compr. Cancer Netw. 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