文章：

胶质母细胞瘤预后预测的免疫相关基因特征识别：基于整合性批量与单细胞RNA测序的深入分析

Identification of an Immune-Related Gene Signature for Prognostic Prediction in Glioblastoma: Insights from Integrated Bulk and Single-Cell RNA Sequencing

原文发布日期：28 May 2025

DOI: 10.3390/cancers17111799

类型: Article

开放获取: 是

英文摘要：

Background:Glioblastoma is a highly malignant brain tumor with limited treatment options and a poor prognosis, largely driven by its complex immune microenvironment. This study aimed to identify and characterize an immune-related gene signature associated with prognosis and immune regulation in glioblastoma.Methods:We performed integrative analyses using bulk and single-cell RNA sequencing data to identify prognostically significant immune-related genes. A five-gene signature (THEMIS2,SIGLEC9,CSTA,LILRB3, andMS4A6A) was derived and its expression patterns were analyzed in association with immune cell infiltration and macrophage subtypes. Functional enrichment and pathway analyses were conducted, followed by drug sensitivity profiling to explore potential therapeutic implications.Results:The five-gene signature was significantly associated with worse survival outcomes and increased immune cell infiltration. Functional analyses revealed involvement in key immune pathways, including antigen presentation, cytokine signaling, and immune cell activation. Single-cell RNA sequencing demonstrated high expression of the signature in tumor-associated macrophages, particularly immune-suppressive and proliferation-associated subtypes. The high expression in proliferation TAMs suggests a role in promoting tumor angiogenesis and growth. Drug sensitivity analysis revealed distinct vulnerabilities between high- and low-risk groups based on signature expression.Conclusions:This Macrophage-Associated Prognostic Signature (MAPS) provides new insights into glioblastoma immunobiology and identifies potential biomarkers and therapeutic targets. It may serve as a valuable tool to guide personalized immunotherapy-based strategies for glioblastoma patients.

摘要翻译： 

背景：胶质母细胞瘤是一种高度恶性的脑肿瘤，治疗选择有限且预后不良，这主要归因于其复杂的免疫微环境。本研究旨在识别并表征与胶质母细胞瘤预后及免疫调控相关的免疫相关基因特征。 方法：我们利用批量及单细胞RNA测序数据进行整合分析，以识别具有预后意义的免疫相关基因。由此推导出一个五基因特征（THEMIS2、SIGLEC9、CSTA、LILRB3和MS4A6A），并分析了其表达模式与免疫细胞浸润及巨噬细胞亚型的关联。随后进行了功能富集和通路分析，并通过药物敏感性分析探索潜在的治疗意义。 结果：该五基因特征与较差的生存结局和增加的免疫细胞浸润显著相关。功能分析显示其参与关键免疫通路，包括抗原呈递、细胞因子信号传导和免疫细胞活化。单细胞RNA测序表明该特征在肿瘤相关巨噬细胞中高表达，尤其是在免疫抑制和增殖相关亚型中。在增殖型肿瘤相关巨噬细胞中的高表达提示其在促进肿瘤血管生成和生长中发挥作用。基于该特征的表达水平，药物敏感性分析揭示了高风险组与低风险组之间存在不同的药物敏感性差异。 结论：这一巨噬细胞相关预后特征为胶质母细胞瘤的免疫生物学提供了新见解，并识别出潜在的生物标志物和治疗靶点。它可能作为一个有价值的工具，用于指导胶质母细胞瘤患者的个体化免疫治疗策略。

原文链接：

Identification of an Immune-Related Gene Signature for Prognostic Prediction in Glioblastoma: Insights from Integrated Bulk and Single-Cell RNA Sequencing