Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China.
Department of Neurosurgery, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang 621000, Sichuan, PR China.
Aging (Albany NY). 2023 Aug 8;15(15):7760-7780. doi: 10.18632/aging.204939.
Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze RNA binding protein (RBP) expression data from The Cancer Genome Atlas (TCGA) for the IDH-wild type GBM cohort. The CIBERSORT algorithm quantified the cellular composition of immune cells and was used to identify key modules associated with CD8+ T cell infiltration. Coexpression networks analysis and protein-protein interaction (PPI) network analysis was used to filter out central RBP genes. Eleven RBP genes, including MYEF2, MAPT, NOVA1, MAP2, TUBB2B, CDH10, TTYH1, PTPRZ1, SOX2, NOVA2 and SCG3, were identified as candidate CD8+ T cell infiltration-associated central genes. A Cox proportional hazards regression model and Kaplan-Meier analysis were applied to identify candidate biomarkers. MYEF2 was selected as a prognostic biomarker based on the results of prognostic analysis. Flow Cytometric Analysis indicated that MYEF2 expression was negatively correlated with dysfunctional CD8+ T cell markers. Kaplan-Meier survival analysis (based on IHC staining) revealed that GBM patients with elevated MYEF2 expression have a better prognosis. Knockdown of MYEF2 in GBM cells via assays was observed to promote cell proliferation and migration. Our study suggests that MYEF2 expression negatively correlates with T cell exhaustion and tumor progression, rendering it a potentially valuable prognostic biomarker for GBM.
胶质母细胞瘤(GBM)是最恶性和最常见的原发性脑肿瘤。在这项研究中,我们对癌症基因组图谱(TCGA)中 IDH 野生型 GBM 队列的 RNA 结合蛋白(RBP)表达数据进行了加权基因共表达网络分析(WGCNA)。CIBERSORT 算法对免疫细胞的细胞组成进行了量化,并用于识别与 CD8+T 细胞浸润相关的关键模块。共表达网络分析和蛋白质-蛋白质相互作用(PPI)网络分析用于筛选出核心 RBP 基因。我们筛选出 11 个 RBP 基因,包括 MYEF2、MAPT、NOVA1、MAP2、TUBB2B、CDH10、TTYH1、PTPRZ1、SOX2、NOVA2 和 SCG3,作为候选的 CD8+T 细胞浸润相关核心基因。应用 Cox 比例风险回归模型和 Kaplan-Meier 分析来识别候选生物标志物。基于预后分析的结果,选择 MYEF2 作为预后生物标志物。流式细胞术分析表明,MYEF2 表达与功能失调的 CD8+T 细胞标志物呈负相关。基于 IHC 染色的 Kaplan-Meier 生存分析表明,MYEF2 高表达的 GBM 患者预后较好。通过实验观察到 MYEF2 在 GBM 细胞中的敲低促进了细胞增殖和迁移。我们的研究表明,MYEF2 表达与 T 细胞耗竭和肿瘤进展呈负相关,使其成为 GBM 有潜在价值的预后生物标志物。