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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Terminal differentiation-induced non-coding RNA (TINCR), initially classified as a long non-coding RNA, encodes a biologically active microprotein (pTINCR) involved in epidermal differentiation and tumor biology. However, the clinicopathological and prognostic relevance of pTINCR expression in cutaneous squamous cell carcinoma (cSCC) remains unclear. We conducted a retrospective case\u2013control study including 116 patients with head and neck cSCC: 58 patients who developed nodal metastasis and 58 non-metastatic controls. pTINCR expression was assessed by immunohistochemistry and analyzed in relation to clinicopathological characteristics and clinical outcomes. Unconditional logistic regression was used to evaluate its association with nodal metastasis. Cox proportional hazards models were additionally used to explore associations with time-to-event outcomes. Negative pTINCR expression was significantly associated with tumor thickness &gt; 6 mm (p &lt; 0.001), poorer histological differentiation (p = 0.002), and higher tumor stage (p = 0.011). In univariate logistic regression, negative pTINCR expression was associated with higher odds of nodal metastasis (OR 2.71, 95% CI 1.27\u20135.77; p = 0.010), but this association was no longer significant after adjustment for established clinicopathological factors (adjusted OR 1.25, 95% CI 0.34\u20134.59; p = 0.736). In Cox analyses, negative pTINCR expression was associated with a shorter time to nodal metastasis (HR 1.88; p = 0.017) and higher tumor-specific mortality (HR 2.02; p = 0.033) in univariate analyses, but not after multivariable adjustment. Tumor budding remained the strongest independent prognostic factor across the evaluated time-to-event outcomes. Loss of pTINCR expression is associated with adverse histopathological features and nodal metastasis in head and neck cSCC, but it does not provide independent prognostic information beyond established clinicopathological factors. pTINCR may therefore serve as a marker of an aggressive tumor phenotype rather than an independent prognostic biomarker.<\/jats:p>","DOI":"10.3390\/ijms27198443","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["pTINCR Expression Is Associated with Tumor Aggressiveness but Does Not Independently Predict Prognosis in Head and Neck Cutaneous Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1644-1655","authenticated-orcid":false,"given":"Raquel","family":"Santos-Juanes","sequence":"first","affiliation":[{"name":"Dermatology Service, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Dermatology Area, Department of Medicine, University of Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5578-3522","authenticated-orcid":false,"given":"Jorge","family":"Santos-Juanes","sequence":"additional","affiliation":[{"name":"Dermatology Service, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"},{"name":"Dermatology Area, Department of Medicine, University of Oviedo, 33006 Oviedo, Spain"},{"name":"Grupo de Investigaci\u00f3n en Dermatolog\u00eda (GRIDER), Universidad de Oviedo, 33006 Oviedo, Spain"},{"name":"Instituto Universitario de Oncolog\u00eda del Principado de Asturias, University of Oviedo, 33011 Oviedo, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-0493","authenticated-orcid":false,"given":"Noelia","family":"Blanco-Agud\u00edn","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Department of Functional Biology, University of Oviedo, 33006 Oviedo, 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