Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Shantou University Medical College, Shantou, Guangdong, China.
Genet Test Mol Biomarkers. 2021 May;25(5):334-345. doi: 10.1089/gtmb.2020.0279. Epub 2021 May 10.
Vascular endothelial growth factors (VEGFs) are important for glioblastoma multiforme (GBM) growth and development. However, the effects of VEGF-targeting drugs in primary GBM remain poorly understood. We aimed to explore the key genes correlated with VEGF expression and prognosis and elucidate their potential implications in GBM anti-VEGF therapy. RNA-seq data with the corresponding clinicopathological information was retrieved from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas. Weighted gene coexpression network analyses was performed on differentially expressed genes to construct coexpression modules and investigate their correlation with VEGFs. Functional enrichment analyses were performed based on the coexpressed genes from the most promising modules. CytoHubba and Kaplan-Meier analyses were implemented to identify the key genes in the modules of interest. The oncomine database, quantitative reverse transcription PCR, and the Human Protein Atlas were used to investigate the expression characteristics of the identified key genes. Four modules (cyan, green, purple, and tan) correlated significantly with VEGF expression. Enrichment analyses suggested that extracellular matrix-receptor interaction, growth factor binding, and the PI3K-Akt pathways were involved in VEGF expression. Four hub genes (, , , ) associated with VEGF were identified. Among them, was regarded as the key gene associated with anti-VEGF therapy. Further, was upregulated in GBM compared to that in normal brain tissues. overexpression was associated with a poor prognosis. was identified as the key gene associated with anti-VEGF therapy and may provide novel insight into GBM targeted therapy.
血管内皮生长因子(VEGFs)在多形性胶质母细胞瘤(GBM)的生长和发展中起着重要作用。然而,VEGF 靶向药物在原发性 GBM 中的作用仍知之甚少。我们旨在探讨与 VEGF 表达和预后相关的关键基因,并阐明它们在 GBM 抗 VEGF 治疗中的潜在意义。从癌症基因组图谱和中国胶质瘤基因组图谱中检索到具有相应临床病理信息的 RNA-seq 数据。对差异表达基因进行加权基因共表达网络分析,构建共表达模块,并研究它们与 VEGFs 的相关性。基于最有前途的模块中的共表达基因进行功能富集分析。利用 CytoHubba 和 Kaplan-Meier 分析鉴定感兴趣模块中的关键基因。Oncomine 数据库、定量逆转录 PCR 和人类蛋白质图谱用于研究鉴定的关键基因的表达特征。四个模块(青色、绿色、紫色和棕褐色)与 VEGF 表达显著相关。富集分析表明,细胞外基质-受体相互作用、生长因子结合和 PI3K-Akt 途径参与了 VEGF 表达。与 VEGF 相关的四个关键基因(、、、)被确定。其中,被认为是与抗 VEGF 治疗相关的关键基因。此外,与正常脑组织相比,在 GBM 中上调。高表达与预后不良相关。被确定为与抗 VEGF 治疗相关的关键基因,可能为 GBM 靶向治疗提供新的见解。