Manuel Molina-Garcia, Maria Jesus Rojas-Lechuga, Cristobal Langdon, Judit Mateu, Jaume Bague, Teresa Torres, Vinicius G de Souza, Manuel Bernal-Sprekelsen, Isam Alobid, Rui Milton Patricio da Silva-Júnior, Susana Puig
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引用次数: 0
Abstract
Background: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis. 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.
Methods: Sixteen SNMM tumors were retrospectively analyzed at the Hospital Clinic of Barcelona. Next-generation sequencing targeted 1392 immuno-oncology-related probes. Log-rank 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.
Results: Among 16 tumors, 107 genes significantly correlated with melanoma-specific survival (MSS) (p < 0.05). 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; p = 0.0051). 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]: 1.503-116.48, p = 0.02). Cluster B tumors displayed upregulated cell cycle genes and reduced infiltration of CD4+, CD8+, Th1, and B cells.
Conclusions: Molecular profiling in SNMM provides prognostic information beyond standard clinical parameters. Cell cycle and immune-related 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-risk patients for tailored therapeutic approaches.
期刊介绍:
International Forum of Allergy & Rhinologyis a peer-reviewed scientific journal, and the Official Journal of the American Rhinologic Society and the American Academy of Otolaryngic Allergy.
International Forum of Allergy Rhinology provides a forum for clinical researchers, basic scientists, clinicians, and others to publish original research and explore controversies in the medical and surgical treatment of patients with otolaryngic allergy, rhinologic, and skull base conditions. The application of current research to the management of otolaryngic allergy, rhinologic, and skull base diseases and the need for further investigation will be highlighted.