Molecular Profiling and Tumor Microenvironment in Sinonasal Mucosal Melanoma as Biomarkers for Enhanced Prognostic Stratification.

IF 6.8 2区 医学 Q1 OTORHINOLARYNGOLOGY
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.

鼻黏膜黑色素瘤的分子分析和肿瘤微环境作为增强预后分层的生物标志物。
背景:鼻窦粘膜黑色素瘤(SNMM)是一种罕见的侵袭性黑色素瘤亚型,预后明显较差。尽管分子表征取得了进展,但SNMM仍然具有临床挑战性,需要详细的分子分析。本研究旨在确定SNMM的分子特征,阐明其预后意义,并为改进治疗提供见解。方法:回顾性分析巴塞罗那医院门诊收治的16例SNMM肿瘤。新一代测序针对1392个免疫肿瘤相关探针。进行Log-rank检验、层次聚类分析(HCA)、Cox回归、差异表达基因、基因集富集分析、xCell算法。统计分析包括描述性统计、临床变量关联和生存分析。结果:在16种肿瘤中,107个基因与黑色素瘤特异性生存(MSS)显著相关(p)。结论:SNMM的分子谱分析提供了超出标准临床参数的预后信息。细胞周期和免疫相关基因表达模式,以及CD4+、CD8+、Th1和B细胞浸润减少,与较差的MSS相关。将分子谱分析与临床分期相结合可以改善风险评估,并帮助识别高危患者,为患者提供量身定制的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.70
自引率
10.90%
发文量
185
审稿时长
6-12 weeks
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.
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