{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:38:34Z","timestamp":1760146714798,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT-Portuguese Foundation for Science and Technology","award":["UIDB\/04501\/2020","POCI-01-0145-FEDER-007628","UIDB\/00051\/2020","UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDB\/04501\/2020","POCI-01-0145-FEDER-007628","UIDB\/00051\/2020","UIDP\/00051\/2020"]}]},{"name":"iBiMED","award":["UIDB\/04501\/2020","POCI-01-0145-FEDER-007628","UIDB\/00051\/2020","UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDB\/04501\/2020","POCI-01-0145-FEDER-007628","UIDB\/00051\/2020","UIDP\/00051\/2020"]}]},{"name":"Cardiovascular R&amp;D Center-UnIC","award":["UIDB\/04501\/2020","POCI-01-0145-FEDER-007628","UIDB\/00051\/2020","UIDP\/00051\/2020"],"award-info":[{"award-number":["UIDB\/04501\/2020","POCI-01-0145-FEDER-007628","UIDB\/00051\/2020","UIDP\/00051\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Targets"],"abstract":"<jats:p>Head and neck cancer (HNC) is the seventh most commonly diagnosed malignancy worldwide, and its incidence is expected to increase in coming years. Current diagnostic methods for HNC are often limited by suboptimal accuracy and speed, which can negatively impact therapeutic decision-making and patient outcomes. To address the shortcomings of conventional diagnostics, biomarker detection has attracted increasing clinical interest as a promising alternative. However, a major challenge is the identification of biomarkers with sufficient accuracy and sensitivity for HNC. The integration of bioinformatics tools with omics data analysis has proven to be a robust approach for biomarker discovery. In this study, we outline a bioinformatics protocol aimed at identifying differentially expressed genes (DEGs) in HNC and evaluating the diagnostic and prognostic relevance of specific genes, including FN1, LGALS3, MMP9, TIMP1, MMP2, and TIMP2, in this pathology. In addition, we performed an enrichment analysis for the genes of interest. The prognostic significance of the selected genes was evaluated in relation to patient survival. This study contributes to the growing body of knowledge by identifying potential biomarkers with diagnostic and prognostic utility in this malignancy.<\/jats:p>","DOI":"10.3390\/targets2040026","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T06:25:16Z","timestamp":1733466316000},"page":"470-480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Biomarkers for Diagnosis and Prognosis of Head and Neck Cancer: Bioinformatics Approach"],"prefix":"10.3390","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9435-487X","authenticated-orcid":false,"given":"Alexandra","family":"Fernandes","sequence":"first","affiliation":[{"name":"iBiMED, Department of Medical Sciences, 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":"iBiMED, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yiu, C.Y., Liu, C.C., Wu, J.Y., Tsai, W.W., Liu, P.H., Cheng, W.J., Chen, J.Y., and Hung, K.C. (2023). Efficacy of the Geriatric Nutritional Risk Index for Predicting Overall Survival in Patients with Head and Neck Cancer: A Meta-Analysis. Nutrients, 15.","DOI":"10.3390\/nu15204348"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vakili, S., Barzegar Behrooz, A., Wichelo, R., Fernades, A., Emwas, A.-H., Jaremko, M., Markowski, J., \u0141os, M.J., Ghavami, S., and Vitorino, R. (2024). Progress in Precision Medicine for Head and Neck Cancer. Preprints, 16.","DOI":"10.20944\/preprints202409.2042.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4065\/83.4.489","article-title":"Head and neck cancer: Changing epidemiology, diagnosis, and treatment","volume":"83","author":"Marur","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100084","DOI":"10.1016\/j.oor.2023.100084","article-title":"Multi-omics approach reveals promising salivary protein markers for head and neck squamous cell carcinoma prognosis","volume":"7","author":"Barros","year":"2023","journal-title":"Oral. Oncol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.soc.2015.03.001","article-title":"Epidemiology of head and neck cancer","volume":"24","author":"Rettig","year":"2015","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.5935\/1808-8694.20130041","article-title":"Head and neck cancer: Causes, prevention and treatment","volume":"79","author":"Galbiatti","year":"2013","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/s41415-022-5166-x","article-title":"Reviewing the epidemiology of head and neck cancer: Definitions, trends and risk factors","volume":"233","author":"Gormley","year":"2022","journal-title":"Br. Dent. J."},{"key":"ref_8","unstructured":"Souza de Oliveira, N., and Rech, N. (2023). Biological aspects of Head and Neck Cancer. Interdiscip. J. Appl. Sci., 7."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e467","DOI":"10.3747\/co.27.6547","article-title":"Delay in diagnosis of patients with head-and-neck cancer in Canada: Impact of patient and provider delay","volume":"27","author":"Kassirian","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2021.05.017","article-title":"Small extracellular vesicle-packaged TGF\u03b21 promotes the reprogramming of normal fibroblasts into cancer-associated fibroblasts by regulating fibronectin in head and neck squamous cell carcinoma","volume":"517","author":"Huang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sheng, S., Guo, B., Wang, Z., Zhang, Z., Zhou, J., and Huo, Z. (2021). Aberrant Methylation and Immune Microenvironment Are Associated With Overexpressed Fibronectin 1: A Diagnostic and Prognostic Target in Head and Neck Squamous Cell Carcinoma. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.753563"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/glycob\/cwu086","article-title":"Galectin-3 in angiogenesis and metastasis","volume":"24","author":"Funasaka","year":"2014","journal-title":"Glycobiology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hara, A., Niwa, M., Noguchi, K., Kanayama, T., Niwa, A., Matsuo, M., Hatano, Y., and Tomita, H. (2020). Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases. Biomolecules, 10.","DOI":"10.3390\/biom10030389"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tan, Y., Zheng, Y., Xu, D., Sun, Z., Yang, H., and Yin, Q. (2021). Galectin-3: A key player in microglia-mediated neuroinflammation and Alzheimer\u2019s disease. Cell Biosci., 11.","DOI":"10.1186\/s13578-021-00592-7"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"578s","DOI":"10.1177\/0145561319893861","article-title":"Evaluation and Prognostic Significance of Galectin-3 Expression in Oral Squamous Cell Carcinoma","volume":"100","author":"Tokmak","year":"2021","journal-title":"Ear Nose Throat J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cai, M., Zheng, Z., Bai, Z., Ouyang, K., Wu, Q., Xu, S., Huang, L., Jiang, Y., Wang, L., and Gao, J. (2022). Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: Potential non-invasive diagnostic and therapeutic biomarkers. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09630-0"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fornieles, G., N\u00fa\u00f1ez, M.I., and Exp\u00f3sito, J. (2023). Matrix Metalloproteinases and Their Inhibitors as Potential Prognostic Biomarkers in Head and Neck Cancer after Radiotherapy. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010527"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5604\/00306657.1202546","article-title":"Matrix metalloproteinases MMP1, MMP2, MMP9 and their tissue inhibitors TIMP1, TIMP2, TIMP3 in head and neck cancer: An immunohistochemical study","volume":"70","author":"Pietruszewska","year":"2016","journal-title":"Otolaryngol. Pol."},{"key":"ref_19","first-page":"2955","article-title":"Screening and identification of potential target genes in head and neck cancer using bioinformatics analysis","volume":"18","author":"Chen","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.clinbiochem.2020.06.008","article-title":"OMICS insights into cancer histology; Metabolomics and proteomics approach","volume":"84","author":"Sarvari","year":"2020","journal-title":"Clin. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100958","DOI":"10.1016\/j.neo.2023.100958","article-title":"Advanced progress of spatial metabolomics in head and neck cancer research","volume":"47","author":"Zhao","year":"2024","journal-title":"Neoplasia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D138","DOI":"10.1093\/nar\/gkad965","article-title":"NCBI GEO: Archive for gene expression and epigenomics data sets: 23-year update","volume":"52","author":"Clough","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s40537-023-00844-y","article-title":"BEST: A web application for comprehensive biomarker exploration on large-scale data in solid tumors","volume":"10","author":"Liu","year":"2022","journal-title":"J. Big Data"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nielsen, H., Petsalaki, E.I., Zhao, L., and St\u00fchler, K. (2019). Predicting eukaryotic protein secretion without signals. Biochim. Biophys. Acta (BBA) Proteins Proteom., 1867.","DOI":"10.1016\/j.bbapap.2018.11.011"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Conesa, A., Madrigal, P., Tarazona, S., Gomez-Cabrero, D., Cervera, A., McPherson, A., Szcze\u015bniak, M.W., Gaffney, D.J., Elo, L.L., and Zhang, X. (2016). A survey of best practices for RNA-seq data analysis. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0881-8"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.semcancer.2014.07.009","article-title":"Focal adhesion signaling and therapy resistance in cancer","volume":"31","author":"Eke","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hyyti\u00e4inen, A., Wahbi, W., V\u00e4yrynen, O., Saarilahti, K., Karihtala, P., Salo, T., and Al-Samadi, A. (2021). Angiogenesis Inhibitors for Head and Neck Squamous Cell Carcinoma Treatment: Is There Still Hope?. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.683570"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kretschmer, M., R\u00fcdiger, D., and Zahler, S. (2021). Mechanical Aspects of Angiogenesis. Cancers, 13.","DOI":"10.3390\/cancers13194987"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1808-8694(15)31289-1","article-title":"The role of matrix extracellular proteins and metalloproteinases in head and neck carcinomas: An updated review","volume":"71","author":"Pereira","year":"2005","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kang, J.J., Ko, A., Kil, S.H., Mallen-St Clair, J., Shin, D.S., Wang, M.B., and Srivatsan, E.S. (2023). EGFR pathway targeting drugs in head and neck cancer in the era of immunotherapy. Biochim. Biophys. Acta Rev. Cancer, 1878.","DOI":"10.1016\/j.bbcan.2022.188827"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xie, J., Huang, L., Lu, Y.G., and Zheng, D.L. (2020). Roles of the Wnt Signaling Pathway in Head and Neck Squamous Cell Carcinoma. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.590912"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fortuna-Costa, A., Gomes, A.M., Kozlowski, E.O., Stelling, M.P., and Pav\u00e3o, M.S. (2014). Extracellular galectin-3 in tumor progression and metastasis. Front. Oncol., 4.","DOI":"10.3389\/fonc.2014.00138"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5284728","DOI":"10.1155\/2020\/5284728","article-title":"Galectin-3 Is a Potential Mediator for Atherosclerosis","volume":"2020","author":"Gao","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_35","first-page":"1799","article-title":"Roles of galectin-3 in the tumor microenvironment and tumor metabolism (Review)","volume":"44","author":"Guo","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.5483\/BMBRep.2020.53.4.020","article-title":"Non-classical role of Galectin-3 in cancer progression: Translocation to nucleus by carbohydrate-recognition independent manner","volume":"53","author":"Kim","year":"2020","journal-title":"BMB Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1016\/j.bmc.2016.07.023","article-title":"Robust design of some selective matrix metalloproteinase-2 inhibitors over matrix metalloproteinase-9 through in silico\/fragment-based lead identification and de novo lead modification: Syntheses and biological assays","volume":"24","author":"Adhikari","year":"2016","journal-title":"Bioorg Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.fsi.2021.10.036","article-title":"Construction of wound repair model and function of recombinant TIMP from Hyriopsis cumingii","volume":"119","author":"An","year":"2021","journal-title":"Fish. Shellfish. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Feser, R., Opperman, R., Nault, B., Maiti, S., Chen, V., and Majumder, M. (2022). Breast Cancer Cell Secretome Analysis to Decipher miRNA Tumor Biology and Discover Potential. Biomarkers. Res. Sq.","DOI":"10.21203\/rs.3.rs-1328838\/v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3872367","DOI":"10.1155\/2020\/3872367","article-title":"The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability","volume":"2020","author":"Li","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/carcin\/bgac037","article-title":"Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer","volume":"43","author":"Peeney","year":"2022","journal-title":"Carcinogenesis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/bs.acc.2021.02.003","article-title":"Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in kidney disease","volume":"105","author":"Zakiyanov","year":"2021","journal-title":"Adv. Clin. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Das, S., Dey, M.K., Devireddy, R., and Gartia, M.R. (2023). Biomarkers in Cancer Detection, Diagnosis, and Prognosis. Sensors, 24.","DOI":"10.3390\/s24010037"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zakari, S., Niels, N.K., Olagunju, G.V., Nnaji, P.C., Ogunniyi, O., Tebamifor, M., Israel, E.N., Atawodi, S.E., and Ogunlana, O.O. (2024). Emerging biomarkers for non-invasive diagnosis and treatment of cancer: A systematic review. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1405267"}],"container-title":["Targets"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2813-3137\/2\/4\/26\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:48:10Z","timestamp":1760114890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2813-3137\/2\/4\/26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["targets2040026"],"URL":"https:\/\/doi.org\/10.3390\/targets2040026","relation":{},"ISSN":["2813-3137"],"issn-type":[{"type":"electronic","value":"2813-3137"}],"subject":[],"published":{"date-parts":[[2024,12,6]]}}}