Background/Objectives: Sinonasal mucosal melanoma (SNMM) is a rare and aggressive melanoma subtype with a notably poor prognosis compared to cutaneous melanoma (CM). Despite advances in molecular characterization, SNMM remains underexplored, posing a clinical challenge and highlighting the need for detailed molecular profiling. This study aimed to identify the molecular features of SNMM, elucidate its clinical behavior and prognostic implications, and provide insights for improved therapeutic strategies.Methods: This retrospective study analyzed 37 primary melanoma tumors diagnosed at the Hospital Clinic of Barcelona. Gene expression was examined using 1402 immuno-oncology-related probes through next-generation sequencing. Hierarchical clustering analysis (HCA), differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and the xCell algorithm were performed. The statistical methods comprised descriptive statistics, clinical variable associations, and survival analyses.Results: HCA revealed two primary clusters. Cluster A exclusively contained CM tumors (20/24), while cluster B included all SNMMs (13/13) and some CMs (4/24). Cluster B showed a higher average age at diagnosis (p= 0.018), higher mitotic index (p= 0.0478), fewerBRAFmutations (p= 0.0017), and poorer melanoma-specific survival (p= 0.0029). Cluster B showed 602 DEGs with cell cycle pathways enriched, immune pathways diminished, lower immune scores (p< 0.0001), and higher stromal scores (p= 0.0074).Conclusions: This study revealed distinct molecular characteristics and an altered tumor microenvironment in SNMMs and certain aggressive CMs. Identifying specific genes and pathways involved in cell cycle progression and immune evasion suggests potential prognostic markers, offering new avenues for enhancing treatment strategies and improving patient survival rates.
背景/目的：鼻腔鼻窦黏膜黑色素瘤（SNMM）是一种罕见且侵袭性强的黑色素瘤亚型，与皮肤黑色素瘤（CM）相比预后显著较差。尽管分子特征研究已取得进展，SNMM的分子机制仍未被充分探索，这构成了临床挑战并凸显了深入分子特征分析的必要性。本研究旨在识别SNMM的分子特征，阐明其临床行为及预后意义，并为改进治疗策略提供见解。 方法：这项回顾性研究分析了巴塞罗那临床医院诊断的37例原发性黑色素瘤肿瘤。通过新一代测序技术，使用1402个免疫肿瘤相关探针检测基因表达。研究进行了层次聚类分析（HCA）、差异表达基因（DEGs）分析、基因集富集分析（GSEA）以及xCell算法分析。统计方法包括描述性统计、临床变量关联分析和生存分析。 结果：HCA揭示了两个主要聚类。聚类A仅包含CM肿瘤（20/24），而聚类B包含所有SNMM（13/13）和部分CM（4/24）。聚类B显示出更高的诊断平均年龄（p=0.018）、更高的有丝分裂指数（p=0.0478）、更少的BRAF突变（p=0.0017）以及更差的黑色素瘤特异性生存率（p=0.0029）。聚类B显示出602个差异表达基因，其中细胞周期通路富集，免疫通路减弱，免疫评分较低（p<0.0001），基质评分较高（p=0.0074）。 结论：本研究揭示了SNMM及某些侵袭性CM具有独特的分子特征和改变的肿瘤微环境。识别参与细胞周期进程和免疫逃逸的特定基因和通路，提示了潜在的预后标志物，为增强治疗策略和提高患者生存率提供了新途径。
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