{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:01:36Z","timestamp":1778630496568,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of neoplasms whose histological derivation comes from the mucous membranes lining the epithelium: the oral cavity, the larynx, the hypopharynx, the nasopharynx, and the oropharynx. The etiopathogenetic mechanisms involving tumor genesis including the alteration of cell proliferation, apoptosis, invasion, migration, and death may involve alterations in the expression of microRNA (miR). To date there have been no systematic reviews with meta-analysis conducted specifically on the role of miR-195 in HNSCC; therefore, our hypothesis was to evaluate if the aberrant expression of miR-195 in HNSCC tissues may represent a prognostic biomarker of survival through the hazard ratio (HR) and relative risk (RR) analysis. The systematic review was designed according to the PRISMA indications; in total, three electronic databases were consulted (PubMed, Scopus, Cochrane Central Trial) including Google Scholar and the gray literature, and a combination of keywords was used such as miR-195 AND HNSCC, microRNA AND HNSCC and miR-195. The meta-analysis and trial sequential analysis were performed using RevMan 5.41 software and TSA software (Cochrane Collaboration, Copenhagen, Denmark). This search identified 1592 articles and, at the end of the selection process, three articles were included. The results of the meta-analysis reported an aggregated risk ratio for overall survival (OS) between the expression of miR-195 at the highest and lowest of 0.36 and 6, respectively, 95% CI: [0.25, 0.51]. Heterogeneity was evaluated through Chi2 = 0.05 df = 2 (p = 0.98) and the Higgins index I2 = 0%. The test for the overall effect was Z = 5.77 (p &lt; 0.00001). The forest plot was in favor of higher OS in patients with high miR-195 expression.<\/jats:p>","DOI":"10.3390\/jpm13020275","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:52:02Z","timestamp":1675219922000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Is the Non-Coding RNA miR-195 a Biodynamic Marker in the Pathogenesis of Head and Neck Squamous Cell Carcinoma? A Prognostic Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-3457","authenticated-orcid":false,"given":"Mario","family":"Dioguardi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8364-2425","authenticated-orcid":false,"given":"Francesca","family":"Spirito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia Apollonia","family":"Caloro","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Nefrologia e Dialisi, Presidio Ospedaliero Scorrano, ASL (Azienda Sanitaria Locale) Lecce, Via Giuseppina Delli Ponti, 73020 Scorrano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-4893","authenticated-orcid":false,"given":"Lorenzo","family":"Lo Muzio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-2521","authenticated-orcid":false,"given":"Stefania","family":"Cantore","sequence":"additional","affiliation":[{"name":"Independent Researcher, Sorriso & Benessere-Ricerca e Clinica, 70129 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-1415","authenticated-orcid":false,"given":"Andrea","family":"Ballini","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-2489","authenticated-orcid":false,"given":"Salvatore","family":"Scacco","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari \u201cAldo Moro\u201d, 70121 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annarita","family":"Malcangi","sequence":"additional","affiliation":[{"name":"Public Local Health Company (Azienda Sanitaria Locale, ASL), B.A.T, 76125 Trani, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Sembronio","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Department, Academic Hospital of Udine, Department of Medical Science, University of Udine, P.le Kolbe 4, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliano","family":"Cascardi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10100 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-4346","authenticated-orcid":false,"given":"Roberto","family":"Arrigoni","sequence":"additional","affiliation":[{"name":"CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Di Cosola","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Nocini","sequence":"additional","affiliation":[{"name":"Unit of Otolaryngology-Head and Neck Department, University of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shinohara, S., Kikuchi, M., Harada, H., Hamaguchi, K., Asato, R., Tamaki, H., Mizuta, M., Hori, R., Kojima, T., and Honda, K. (2021). Clinicopathological Characteristics and Survival Outcomes of Patients with Buccal Squamous Cell Carcinoma: Results of a Multi-Institutional Study. Medicina, 57.","DOI":"10.3390\/medicina57121361"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.oooo.2021.08.023","article-title":"Oral squamous cell carcinoma in patients aged 45 and younger: Prognosis, survival, and quality of life","volume":"133","author":"Farhat","year":"2021","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1158\/1055-9965.EPI-21-0922","article-title":"Characterization of epigenomic alterations in HPV16+ head and neck squamous cell carcinomas","volume":"31","author":"Berglund","year":"2022","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7312611","DOI":"10.1155\/2021\/7312611","article-title":"Overview of Candida albicans and Human Papillomavirus (HPV) Infection Agents and their Biomolecular Mechanisms in Promoting Oral Cancer in Pediatric Patients","volume":"2021","author":"Muzio","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bajbouj, K., Al-Ali, A., Ramakrishnan, R.K., Saber-Ayad, M., and Hamid, Q. (2021). Histone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111701"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hasbullah, H.H., and Musa, M. (2021). Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111941"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13045-021-01169-0","article-title":"Targeting mutant p53 for cancer therapy: Direct and indirect strategies","volume":"14","author":"Hu","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1002\/ijc.33912","article-title":"Complexity against current cancer research\u2014Are we on the wrong track?","volume":"150","author":"Kasikci","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"602","DOI":"10.52586\/4970","article-title":"Methylation alterations and advance of treatment in lymphoma","volume":"26","author":"Liu","year":"2021","journal-title":"Front. Biosci.-Landmark"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"708765","DOI":"10.3389\/fonc.2021.708765","article-title":"Tumor Suppressor miRNA in Cancer Cells and the Tumor Microenvironment: Mechanism of Deregulation and Clinical Implications","volume":"11","author":"Otmani","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Perri, P., Ponzoni, M., Corrias, M.V., Ceccherini, I., Candiani, S., and Bachetti, T. (2021). A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma. Cancers, 13.","DOI":"10.3390\/cancers13215528"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Limongelli, L., Cascardi, E., Capodiferro, S., Favia, G., Corsalini, M., Tempesta, A., and Maiorano, E. (2020). Multifocal Amelanotic Melanoma of the Hard Palate: A Challenging Case. Diagnostics, 10.","DOI":"10.3390\/diagnostics10060424"},{"key":"ref_14","first-page":"1","article-title":"Real-world histopathological approach to malignancy of undefined primary origin (MUO) to diagnose cancers of unknown primary (CUPs)","volume":"8","author":"Pisacane","year":"2022","journal-title":"Virchows Arch."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1038\/s41467-021-22643-w","article-title":"Cancer of unknown primary stem-like cells model multi-organ metastasis and unveil liability to MEK inhibition","volume":"12","author":"Verginelli","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.omto.2021.12.001","article-title":"The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma","volume":"24","author":"Jiang","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3390\/cancers2020653","article-title":"MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell Carcinoma (OSCC)","volume":"2","author":"Shiiba","year":"2010","journal-title":"Cancers"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dioguardi, M., Spirito, F., Sovereto, D., Alovisi, M., Troiano, G., Aiuto, R., Garcovich, D., Crincoli, V., Laino, L., and Cazzolla, A.P. (2022). MicroRNA-21 Expression as a Prognostic Biomarker in Oral Cancer: Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19063396"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dioguardi, M., Spirito, F., Sovereto, D., Alovisi, M., Aiuto, R., Garcovich, D., Crincoli, V., Laino, L., Cazzolla, A.P., and Caloro, G.A. (2022). The Prognostic Role of miR-31 in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis with Trial Sequential Analysis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19095334"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dioguardi, M., Spirito, F., Sovereto, D., La Femina, L., Campobasso, A., Cazzolla, A.P., Di Cosola, M., Zhurakivska, K., Cantore, S., and Ballini, A. (2022). Biological Prognostic Value of miR-155 for Survival Outcome in Head and Neck Squamous Cell Carcinomas: Systematic Review, Meta-Analysis and Trial Sequential Analysis. Biology, 11.","DOI":"10.3390\/biology11050651"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1186\/s13018-021-02538-8","article-title":"Expression of miR-195 and its target gene Bcl-2 in human intervertebral disc degeneration and their effects on nucleus pulposus cell apoptosis","volume":"16","author":"Lin","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_22","first-page":"6871","article-title":"microRNA-195-Cdc42 axis acts as a prognostic factor of esophageal squamous cell carcinoma","volume":"7","author":"Sun","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.3892\/or.2017.5875","article-title":"MicroRNA-195 inhibits growth and invasion of laryngeal carcinoma cells by directly targeting DCUN1D1","volume":"38","author":"Shuang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_24","first-page":"e1000100","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration","volume":"6","author":"Liberati","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dioguardi, M., Cantore, S., Scacco, S., Quarta, C., Sovereto, D., Spirito, F., Alovisi, M., Troiano, G., Aiuto, R., and Garcovich, D. (2022). From Bench to Bedside in Precision Medicine: Diabetes Mellitus and Peri-Implantitis Clinical Indices with a Short-Term Follow-Up: A Systematic Review and Meta-Analysis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020235"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dioguardi, M., Cantore, S., Sovereto, D., La Femina, L., Caloro, G.A., Spirito, F., Scacco, S., Di Cosola, M., Lo Muzio, L., and Troiano, G. (2022). Potential Role of miR-196a and miR-196b as Prognostic Biomarkers of Survival in Head and Neck Squamous Cell Carcinoma: A Systematic Review, Meta-Analysis and Trial Sequential Analysis. Life, 12.","DOI":"10.3390\/life12081269"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dioguardi, M., Cantore, S., Sovereto, D., La Femina, L., Spirito, F., Caloro, G.A., Caroprese, M., Maci, M., Scacco, S., and Lo Muzio, L. (2022). Does miR-197 Represent a Valid Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma (HNSCC)? A Systematic Review and Trial Sequential Analysis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12091436"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1745-6215-8-16","article-title":"Practical methods for incorporating summary time-to-event data into meta-analysis","volume":"8","author":"Tierney","year":"2007","journal-title":"Trials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/jnci\/djy088","article-title":"Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): An Abridged Explanation and Elaboration","volume":"110","author":"Sauerbrei","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/jrsm.1313","article-title":"Using systematic reviews in guideline development: The GRADE approach","volume":"10","author":"Zhang","year":"2018","journal-title":"Res. Synth. Methods"},{"key":"ref_31","first-page":"315","article-title":"Clinical significance of miRNA-195 expression in patients with laryngeal carcinoma","volume":"24","author":"Ding","year":"2019","journal-title":"J. BUON"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jia, L.-F., Wei, S.-B., Gong, K., Gan, Y.-H., and Yu, G.-Y. (2013). Prognostic implications of micoRNA miR-195 expression in human tongue squamous cell carcinoma. PloS ONE, 8.","DOI":"10.1371\/journal.pone.0056634"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"772514","DOI":"10.3389\/fbioe.2022.772514","article-title":"Pro-Angiogenesis Role of LINC00662 from Esophageal Squamous Cell Carcinoma Cells-Derived Extracellular Vehicles","volume":"10","author":"Li","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"112885","DOI":"10.1016\/j.biopha.2022.112885","article-title":"Roles and mechanisms of miR-195-5p in human solid cancers","volume":"150","author":"Xu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Riley, R.D., Hayden, J.A., Steyerberg, E.W., Moons, K.G., Abrams, K., Kyzas, P.A., Malats, N., Briggs, A., Schroter, S., and Altman, D.G. (2013). Prognosis Research Strategy (PROGRESS) 2: Prognostic factor research. PLoS Med., 10.","DOI":"10.1371\/journal.pmed.1001380"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/2\/275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:42Z","timestamp":1760120382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/2\/275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,31]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jpm13020275"],"URL":"https:\/\/doi.org\/10.3390\/jpm13020275","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,31]]}}}