{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:16:53Z","timestamp":1788412613339,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011913","name":"Kaohsiung Veterans General Hospital","doi-asserted-by":"crossref","award":["KSVGH115-098"],"award-info":[{"award-number":["KSVGH115-098"]}],"id":[{"id":"10.13039\/501100011913","id-type":"DOI","asserted-by":"crossref"}]},{"award":["KSVGH115-098"],"award-info":[{"award-number":["KSVGH115-098"]}],"id":[{"id":"https:\/\/ror.org\/04jedda80","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Health and Welfare","award":["21020358-00114001-8"],"award-info":[{"award-number":["21020358-00114001-8"]}]},{"award":["21020358-00114001-8"],"award-info":[{"award-number":["21020358-00114001-8"]}],"id":[{"id":"https:\/\/ror.org\/024w0ge69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Death-associated protein kinase 1 (DAPK1) is a key regulator of apoptosis and immune responses; however, its prognostic significance in oral cancer remains insufficiently characterized. This study investigated the prognostic relevance of DAPK1 in oral squamous cell carcinoma (OSCC) and examined its associations with immune infiltration and apoptosis-related signaling pathways. Methods: A retrospective translational study design was employed, integrating TCGA-based expression and methylation analyses of 528 head and neck squamous cell carcinoma (HNSCC) tumors, UALCAN epigenetic profiling, GeneMANIA protein\u2013protein interaction mapping, TIMER 2.0 immune correlation analyses in 422 HPV-negative HNSCC patients, and multiplex immunofluorescence validation using a tissue microarray cohort of 82 patients with histologically confirmed OSCC, of whom 75 were eligible for the final analysis at Kaohsiung Veterans General Hospital, Taiwan. Results: In vitro validation using Western blot analysis in FaDu cells showed that epidermal growth factor receptor (EGFR) inhibition with gefitinib induced upregulation of DAPK1 protein expression at 10 \u03bcM and increased total caspase-3 expression. Higher DAPK1 signal in whole-field quantification was associated with increased CD4+ and CD8+ T-cell infiltration and enrichment of apoptosis-related pathways. Patients with high DAPK1 expression demonstrated a consistent protective trend for overall survival in a pre-specified fully adjusted primary model (adjusted HR = 0.51, 95% CI: 0.21\u20131.21, p = 0.126), and exhibited significantly improved survival in a secondary parsimonious model (adjusted HR = 0.41, 95% CI: 0.18\u20130.91, p = 0.029). Multiplex immunofluorescence further confirmed stronger DAPK1 and caspase-3 staining, along with denser lymphocytic infiltration within the tumor microenvironment. Conclusions: Collectively, these findings suggest that DAPK1 is associated with apoptosis-related signaling, increased immune-cell infiltration, and favorable clinical outcomes in OSCC, although its independent prognostic value requires validation in larger cohorts.<\/jats:p>","DOI":"10.3390\/cells15171566","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"1566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Relevance and Immune Correlates of DAPK1 Expression and CD4+\/CD8+ T-Cell Infiltration in Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8332-8970","authenticated-orcid":false,"given":"Hsiao-Chi","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"},{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 907101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Keng-Ming","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"},{"name":"Department of Otolaryngology, Head and Neck Surgery, Pingtung Veterans General Hospital, Pingtung 900053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Ching-Chih","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"},{"name":"School of Medicine, National Defense Medical Center, Taipei 114036, Taiwan"},{"name":"Institute of Hospital and Health Care Administration, National Yang Ming Chao Tung University, Taipei 112304, Taiwan"},{"name":"Department of Early Childhood Care and Education, Cheng Shiu University, Kaohsiung 833301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1192\/bjp.bp.111.107961","article-title":"Betel-quid dependence and oral potentially malignant disorders in six Asian countries","volume":"201","author":"Lee","year":"2012","journal-title":"Br. 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