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This study investigates the prognostic and biological significance of <jats:italic>DMD<\/jats:italic> expression in head and neck squamous cell carcinoma (HNSCC). Analysis of The Cancer Genome Atlas (TCGA) data revealed that high <jats:italic>DMD<\/jats:italic> expression correlates with improved overall (median survival difference: 22\u00a0months, p\u2009=\u20090.0083) and progression-free (p\u2009=\u20090.0237) survival. The Dp71ab transcript is most strongly associated with better outcomes (median overall survival: 42\u00a0months, p\u2009=\u20090.0007). Notably, <jats:italic>DMD<\/jats:italic> expression levels stratify HPV-positive patients, identifying a <jats:italic>DMD<\/jats:italic> low\/HPV-positive subgroup with poor outcomes. Immunohistochemical analysis of 50 HNSCC tissue cases confirmed dystrophin localisation in the nucleus and cytoplasm, with high nuclear expression linked to longer overall survival (mean difference: 31\u00a0months, p\u2009=\u20090.0497). Functional assays in HNSCC cells showed that Dp71ab overexpression disrupts nuclear morphology and reduces proliferation. Differential gene expression analysis additionally identified 388 upregulated and 30 downregulated genes, with pathways linked to muscle processes, ribosome biogenesis and non-coding RNA regulation. These findings highlight <jats:italic>DMD<\/jats:italic> as a potential biomarker and\/or therapeutic target in HNSCC, warranting further mechanistic studies of Dp71 isoforms.<\/jats:p>","DOI":"10.1038\/s41598-025-94221-9","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T05:07:29Z","timestamp":1743224849000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Duchenne muscular dystrophy gene product expression is associated with survival in head and neck squamous cell carcinoma"],"prefix":"10.1038","volume":"15","author":[{"given":"Leanne","family":"Jones","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonika","family":"Divakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael","family":"Hamarneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Ameerally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Anthony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"94221_CR1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1474-4422(03)00585-4","volume":"2","author":"F Muntoni","year":"2003","unstructured":"Muntoni, F., Torelli, S. & Ferlini, A. 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