Chen Jianan, Wu Qiong, Berglund Anders E, Macaulay Robert J, Mulé James J, Etame Arnold B
Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA.
Cancers (Basel). 2025 May 28;17(11):1799. doi: 10.3390/cancers17111799.
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. We performed integrative analyses using bulk and single-cell RNA sequencing data to identify prognostically significant immune-related genes. A five-gene signature (, , , , and ) 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. 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. 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.
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较差，这在很大程度上是由其复杂的免疫微环境所驱动的。本研究旨在识别和表征与胶质母细胞瘤预后和免疫调节相关的免疫相关基因特征。我们使用批量和单细胞RNA测序数据进行综合分析，以识别具有预后意义的免疫相关基因。得出了一个五基因特征（、、、和），并分析了其表达模式与免疫细胞浸润和巨噬细胞亚型的关系。进行了功能富集和通路分析，随后进行药物敏感性分析以探索潜在的治疗意义。该五基因特征与较差的生存结果和增加的免疫细胞浸润显著相关。功能分析表明其参与了关键的免疫通路，包括抗原呈递、细胞因子信号传导和免疫细胞激活。单细胞RNA测序显示该特征在肿瘤相关巨噬细胞中高表达，特别是免疫抑制和增殖相关亚型。增殖性肿瘤相关巨噬细胞中的高表达表明其在促进肿瘤血管生成和生长中起作用。药物敏感性分析揭示了基于特征表达的高风险和低风险组之间不同的易感性。这种巨噬细胞相关预后特征（MAPS）为胶质母细胞瘤免疫生物学提供了新的见解，并识别出潜在的生物标志物和治疗靶点。它可能作为一种有价值的工具，来指导针对胶质母细胞瘤患者的基于个性化免疫治疗的策略。
