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葡萄膜黑色素瘤中基于炎症反应相关基因的分子亚型构建与验证及一种新型预后标志物

Construction and Verification of the Molecular Subtype and a Novel Prognostic Signature Based on Inflammatory Response-Related Genes in Uveal Melanoma.

作者信息

Zhang Feng, Deng Yan, Wang Dong, Wang Shuai

机构信息

Department of Ophthalmology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou 434020, China.

Department of Hepatobiliary Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou 434020, China.

出版信息

J Clin Med. 2023 Jan 21;12(3):861. doi: 10.3390/jcm12030861.

DOI:10.3390/jcm12030861
PMID:36769510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9918108/
Abstract

The significance of inflammation in tumorigenesis and progression has become prominent. This study aimed to construct and validate the molecular subtype and a novel prognostic signature based on inflammatory response-related genes in uveal melanoma (UM). Patients from the TCGA, GSE84976, and GSE22138 UM cohorts were enrolled. According to the consensus cluster analysis, patients were divided into two molecular subtypes, namely IC1 and IC2. Survival curves showed that patients in IC1 had a better prognosis. The IC2 subgroup had higher levels of immune cell infiltration and more enriched immunological pathways. There were statistical differences in the immune-inflammation microenvironment, immune checkpoint genes expression, and drug sensitivity. The prognostic signature constructed based on inflammatory response-related genes exhibited a stable predictive power. Multivariate analysis confirmed that the signature was a prognostic factor independent of clinical characteristics. Functional analyses showed that the high-risk group was associated with immunological response, inflammatory cell activation, and tumor-related signal pathways. The riskscore had a negative relationship with tumor purity and was positively correlated with immune and stromal scores. Furthermore, the prognostic signature could sensitively predict the response to drug treatments. In conclusion, the prognostic signature might aid in stratifying patients at risk premised on the prognosis and immunotherapy sensitivity.

摘要

炎症在肿瘤发生和进展中的重要性已日益凸显。本研究旨在构建并验证基于葡萄膜黑色素瘤（UM）炎症反应相关基因的分子亚型和一种新的预后特征。纳入了来自TCGA、GSE84976和GSE22138 UM队列的患者。根据一致性聚类分析，患者被分为两种分子亚型，即IC1和IC2。生存曲线显示，IC1组患者预后较好。IC2亚组具有更高水平的免疫细胞浸润和更丰富的免疫途径。在免疫炎症微环境、免疫检查点基因表达和药物敏感性方面存在统计学差异。基于炎症反应相关基因构建的预后特征表现出稳定的预测能力。多因素分析证实该特征是一个独立于临床特征的预后因素。功能分析表明，高危组与免疫反应、炎症细胞激活和肿瘤相关信号通路有关。风险评分与肿瘤纯度呈负相关，与免疫和基质评分呈正相关。此外，预后特征可以敏感地预测药物治疗反应。总之，该预后特征可能有助于根据预后和免疫治疗敏感性对高危患者进行分层。

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