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Despite molecular characterization advances, SNMM remains clinically challenging, highlighting the need for detailed molecular profiling. This study aimed to identify the molecular features of SNMM, elucidate its prognostic implications, and provide insights for improved therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixteen SNMM tumors were retrospectively analyzed at the Hospital Clinic of Barcelona. Next\u2010generation sequencing targeted 1392 immuno\u2010oncology\u2010related probes. Log\u2010rank test, hierarchical clustering analysis (HCA), Cox regression, differentially expressed genes, gene set enrichment analysis, and the xCell algorithm were performed. Statistical analyses comprised descriptive statistics, clinical variable associations, and survival analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 16 tumors, 107 genes significantly correlated with melanoma\u2010specific survival (MSS) (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). HCA based on these genes revealed two clusters: Cluster B showed poorer prognosis (median MSS: 11.73 months; Q1: 8.74, Q3: 30.78) compared to Cluster A (median MSS: 81.74 months; Q1: 32.82, Q3: 92.44; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0051). Cox regression identified staging and molecular clustering as independent MSS predictors, with Cluster B exhibiting a hazard ratio of 13.23 (95% confidence intervals [CI]: 1.503\u2013116.48, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.02). Cluster B tumors displayed upregulated cell cycle genes and reduced infiltration of CD4+, CD8+, Th1, and B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Molecular profiling in SNMM provides prognostic information beyond standard clinical parameters. Cell cycle and immune\u2010related gene expression patterns, together with decreased infiltration of CD4+, CD8+, Th1, and B cells, correlate with poorer MSS. Integrating molecular profiling with clinical staging could improve risk assessment and help identify high\u2010risk patients for tailored therapeutic approaches.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.23606","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T07:11:20Z","timestamp":1747638680000},"page":"1082-1093","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Profiling and Tumor Microenvironment in Sinonasal Mucosal Melanoma as Biomarkers for Enhanced Prognostic Stratification"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4218-9756","authenticated-orcid":false,"given":"Manuel","family":"Molina\u2010Garcia","sequence":"first","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Department of Medicine Faculty of Medicine and Health Sciences Universitat de Barcelona (UB)  Barcelona Spain"},{"name":"Melanoma Unit, Dermatology Department Hospital Clinic of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-5167","authenticated-orcid":false,"given":"Maria Jesus","family":"Rojas\u2010Lechuga","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Department of Medicine Faculty of Medicine and Health Sciences Universitat de Barcelona (UB)  Barcelona Spain"},{"name":"Otorhinolaryngology Department Hospital Clinic of Barcelona CIBERES  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristobal","family":"Langdon","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Department Hospital Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0586-1200","authenticated-orcid":false,"given":"Judit","family":"Mateu","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Melanoma Unit, Dermatology Department Hospital Clinic of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaume","family":"Bague","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Melanoma Unit, Dermatology Department Hospital Clinic of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Torres","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Melanoma Unit, Dermatology Department Hospital Clinic of Barcelona  Barcelona Spain"},{"name":"Centre of Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinicius G.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Bernal\u2010Sprekelsen","sequence":"additional","affiliation":[{"name":"Department of Medicine Faculty of Medicine and Health Sciences Universitat de Barcelona (UB)  Barcelona Spain"},{"name":"Otorhinolaryngology Department Hospital Clinic of Barcelona CIBERES  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isam","family":"Alobid","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona 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