{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:17:22Z","timestamp":1793863042901,"version":"4.6.1"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Head and Neck Squamous Cell Carcinoma (HNSCC) includes cancers from the oral cavity, larynx, and oropharynx and is the sixth-most common cancer worldwide. MicroRNAs are small non-coding RNAs for which altered expression has been demonstrated in pathological processes, such as cancer. The objective of our study was to evaluate the different expression profile in HNSCC subtypes and the prognostic value that one or several miRNAs may have. Materials and Methods: Data from The Cancer Genome Atlas Program-Head and Neck Squamous Cell Carcinoma (TCGA-HNSCC) patients were collected. Differential expression analysis was conducted by edge R-powered TCGAbiolinks R package specific function. Enrichment analysis was developed with Diana Tool miRPath 3.0. Kaplan-Meier survival estimators were used, followed by log-rank tests to compute significance. Results: A total of 127 miRNAs were identified with differential expression level in HNSCC; 48 of them were site-specific and, surprisingly, only miR-383 showed a similar deregulation in all locations studied (tonsil, mouth, floor of mouth, cheek mucosa, lip, tongue, and base of tongue). The most probable affected pathways based on miRNAs interaction levels were protein processing in endoplasmic reticulum, proteoglycans in cancer (p &lt; 0.01), Hippo signaling pathway (p &lt; 0.01), and Transforming growth factor-beta (TGF-beta) signaling pathway (p &lt; 0.01). The survival analysis highlighted 38 differentially expressed miRNAs as prognostic biomarkers. The miRNAs with a greater association between poor prognosis and altered expression (p &lt; 0.001) were miR-137, miR-125b-2, miR-26c, and miR-1304. Conclusions: In this study we have determined miR-137, miR-125b-2, miR-26c, and miR-1304 as novel powerful prognosis biomarkers. Furthermore, we have depicted the miRNAs expression patterns in tumor patients compared with normal subjects using the TCGA-HNSCC cohort.<\/jats:p>","DOI":"10.3390\/medicina56100535","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of Prognosis Associated microRNAs in HNSCC Subtypes Based on TCGA Dataset"],"prefix":"10.3390","volume":"56","author":[{"given":"Cintia","family":"Chamorro Petronacci","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Dentistry, Health Research, Institute of Santiago de Compostela (Instituto de Investigaci\u00f3n Sanitaria de Santiago, IDIS), Oral Medicine, Oral Surgery and Implantology University, Santiago de Compostela University, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel","family":"Garc\u00eda Garc\u00eda","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Health Research, Institute of Santiago de Compostela (Instituto de Investigaci\u00f3n Sanitaria de Santiago, IDIS), Oral Medicine, Oral Surgery and Implantology University, Santiago de Compostela University, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pad\u00edn Iruegas","sequence":"additional","affiliation":[{"name":"Department of Functional Biology and Health Sciences, Faculty of Physiotherapy, Human Anatomy and Embryology Area, Vigo University, 36001 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Rivas Mundi\u00f1a","sequence":"additional","affiliation":[{"name":"Pathology and Therapeutic Unity, Faculty of Medicine and Dentistry, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-4703","authenticated-orcid":false,"given":"Alejandro","family":"Lorenzo Pouso","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Health Research, Institute of Santiago de Compostela (Instituto de Investigaci\u00f3n Sanitaria de Santiago, IDIS), Oral Medicine, Oral Surgery and Implantology University, Santiago de Compostela University, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-9868","authenticated-orcid":false,"given":"Mario","family":"P\u00e9rez Say\u00e1ns","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Health Research, Institute of Santiago de Compostela (Instituto de Investigaci\u00f3n Sanitaria de Santiago, IDIS), Oral Medicine, Oral Surgery and Implantology University, Santiago de Compostela University, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41419-019-1769-9","article-title":"Clinical update on head and neck cancer: Molecular biology and ongoing challenges","volume":"10","author":"Alsahafi","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA A Cancer J. Clin."},{"key":"ref_3","first-page":"314","article-title":"Prognostic factors of survival rate in oral squamous cell carcinoma: Clinical, histologic, genetic and molecular concepts","volume":"18","author":"Taghavi","year":"2015","journal-title":"Arch. Iran. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neo.2018.12.002","article-title":"Genome-Wide Analysis of Head and Neck Squamous Cell Carcinomas Reveals HPV, TP53, Smoking and Alcohol-Related Allele-Based Acquired Uniparental Disomy Genomic Alterations","volume":"21","author":"Tuna","year":"2019","journal-title":"Neoplasia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrc.2018.11","article-title":"The molecular landscape of head and neck cancer","volume":"18","author":"Leemans","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-0034-1397344","article-title":"Overview of MicroRNA Biology","volume":"35","author":"Mohr","year":"2015","journal-title":"Semin. Liver Dis."},{"key":"ref_7","first-page":"433","article-title":"Current trends in miRNAs and their relationship with oral squamous cell carcinoma","volume":"41","author":"Pilar","year":"2011","journal-title":"J. Oral Pathol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94528","DOI":"10.18632\/oncotarget.21786","article-title":"A six-mRNA signature model for the prognosis of head and neck squamous cell carcinoma","volume":"8","author":"Guo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/03009734.2018.1439551","article-title":"MicroRNA meta-signature of oral cancer: Evidence from a meta-analysis","volume":"123","author":"Zeljic","year":"2018","journal-title":"Upsala J. Med Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.critrevonc.2013.07.012","article-title":"microRNAs are important players in head and neck carcinoma: A review","volume":"88","author":"Janiszewska","year":"2013","journal-title":"Crit. Rev. Oncol."},{"key":"ref_11","first-page":"1","article-title":"MicroRNAs as Important Players and Biomarkers in Oral Carcinogenesis","volume":"2015","author":"Min","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_12","first-page":"102","article-title":"Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA-122 levels without affecting other microRNAs in plasma","volume":"43","author":"Ottosen","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10637-016-0407-y","article-title":"Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors","volume":"35","author":"Beg","year":"2016","journal-title":"Investig. New Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Say\u00e1ns, M., Chamorro-Petronacci, C.M., Lorenzo-Pouso, A.I., Iruegas, E.P., Carri\u00f3n, A.B., Pe\u00f1aranda, J.M.S., and Garc\u00eda-Garc\u00eda, A. (2019). Comprehensive Genomic Review of TCGA Head and Neck Squamous Cell Carcinomas (HNSCC). J. Clin. Med., 8.","DOI":"10.3390\/jcm8111896"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","article-title":"TCGAbiolinks: An R\/Bioconductor package for integrative analysis of TCGA data","volume":"44","author":"Colaprico","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W460","DOI":"10.1093\/nar\/gkv403","article-title":"DIANA-miRPath v3.0: Deciphering microRNA function with experimental support","volume":"43","author":"Vlachos","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.oraloncology.2015.01.008","article-title":"MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: A systematic review and meta-analysis","volume":"51","author":"Jamali","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_19","first-page":"52","article-title":"2016 Oral, Head and Neck Cancer Awareness Week: April 10\u201316","volume":"95","author":"Nathan","year":"2016","journal-title":"Ear Nose Throat J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e14922","DOI":"10.1097\/MD.0000000000014922","article-title":"miRNAs expression of oral squamous cell carcinoma patients","volume":"98","author":"Petronacci","year":"2019","journal-title":"Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.31557\/APJCP.2020.21.6.1841","article-title":"Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma","volume":"21","author":"Koushki","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1002\/cam4.718","article-title":"Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas","volume":"5","author":"Wong","year":"2016","journal-title":"Cancer Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Santos-De-Frutos, K., Segrelles, C., and Lorz, C. (2019). Hippo Pathway and YAP Signaling Alterations in Squamous Cancer of the Head and Neck. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122131"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.1038\/onc.2010.306","article-title":"TGF\u03b2 signaling in head and neck squamous cell carcinoma","volume":"29","author":"White","year":"2010","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"43177","DOI":"10.18632\/oncotarget.9506","article-title":"Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck","volume":"7","author":"Flowers","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jdsr.2020.04.001","article-title":"MicroRNA\u2019s\u2014The vibrant performers in the oral cancer scenario","volume":"56","author":"Solomon","year":"2020","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/jop.12667","article-title":"Oral cancer databases: A comprehensive review","volume":"47","author":"Sarode","year":"2017","journal-title":"J. Oral Pathol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.2174\/1871520618666180411110036","article-title":"Translational Research: A Future Strategy for Managing Squamous Cell Carcinoma of the Head and Neck?","volume":"18","author":"Caponigro","year":"2019","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"451","DOI":"10.7754\/Clin.Lab.2015.150802","article-title":"MicroRNAs as a Novel Class of Diagnostic Biomarkers in Detection of Oral Carcinoma: A Meta-Analysis Study","volume":"62","author":"Lin","year":"2016","journal-title":"Clin Lab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1600-0714.2011.01084.x","article-title":"Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these microRNAs in oral lichen planus","volume":"41","author":"Danielsson","year":"2011","journal-title":"J. Oral Pathol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1111\/jop.12300","article-title":"Altered levels of miR-21, miR-125b-2*, miR-138, miR-155, miR-184, and miR-205 in oral squamous cell carcinoma and association with clinicopathological characteristics","volume":"44","author":"Manikandan","year":"2014","journal-title":"J. Oral Pathol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1365-2559.2012.04242.x","article-title":"Differential expression of microRNAs miR-21, miR-31, miR-203, miR-125a-5p and miR-125b and proteins PTEN and p63 in verrucous carcinoma of the head and neck","volume":"61","author":"Odar","year":"2012","journal-title":"Histopathology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.oraloncology.2016.03.017","article-title":"microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection","volume":"57","author":"He","year":"2016","journal-title":"Oral Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/jcb.22995","article-title":"miR-21 downregulates the tumor suppressor P12CDK2AP1 and Stimulates Cell Proliferation and Invasion","volume":"112","author":"Zheng","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/j.prp.2018.09.010","article-title":"The expression and biological information analysis of miR-375-3p in head and neck squamous cell carcinoma based on 1825 samples from GEO, TCGA, and peer-reviewed publications","volume":"214","author":"Cen","year":"2018","journal-title":"Pathol. Res. Pr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ijom.2013.04.016","article-title":"MicroRNA-375 sensitizes tumour necrosis factor-alpha (TNF-\u03b1)-induced apoptosis in head and neck squamous cell carcinoma in vitro","volume":"42","author":"Wang","year":"2013","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_37","first-page":"1775","article-title":"MiR-21\/miR-375 ratio is an independent prognostic factor in patients with laryngeal squamous cell carcinoma","volume":"5","author":"Hu","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s11010-018-3336-6","article-title":"DNA methylation regulated microRNAs in HPV-16-induced head and neck squamous cell carcinoma (HNSCC)","volume":"448","author":"Sannigrahi","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Affinito, O., Pane, K., Smaldone, G., Orlandella, F.M., Mirabelli, P., Beneduce, G., Parasole, R., Ripaldi, M., Salvatore, M., and Franzese, M. (2020). lncRNAs\u2013mRNAs Co\u2013Expression Network Underlying Childhood B\u2013Cell Acute Lymphoblastic Leukaemia: A Pilot Study. Cancers, 12.","DOI":"10.3390\/cancers12092489"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/14756366.2018.1426574","article-title":"Differential expression of snoRNAs in oral squamous cell carcinomas: New potential diagnostic markers","volume":"33","author":"Petronacci","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5824","DOI":"10.1002\/anie.201502146","article-title":"Tumor-targeted Delivery of Anti-microRNA for Cancer Therapy: pHLIP is Key","volume":"54","author":"Wagner","year":"2015","journal-title":"Angew. Chem. Int. Ed."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/10\/535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:20:16Z","timestamp":1760178016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/10\/535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,13]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["medicina56100535"],"URL":"https:\/\/doi.org\/10.3390\/medicina56100535","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,13]]}}}