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内皮细胞在胶质母细胞瘤中的预后价值探讨及验证

Exploration and Verification of Prognostic Value of Endothelial Cells in Glioblastoma

  • 摘要:
    目的 探讨并验证胶质母细胞瘤中内皮细胞的预后价值。
    方法 通过对TCGA和CGGA数据库进行生物信息分析,按照一系列标准筛选GBM单细胞数据中内皮细胞相关标志物并进行单因素Cox回归分析,获取并筛选内皮细胞预后相关标志物,构建内皮细胞相关预后风险评分。qPCR实验验证预后相关标志物在GBM组织及瘤周正常脑组织中的表达差异。Kaplan-Meier法构建生存曲线以鉴定该预后风险评分的预后效能。
    结果 共筛选获得2 115个GBM预后相关基因,其中1 494个上调,621个下调。GBM单细胞测序分析降维后共获得7群细胞,分别为AC样肿瘤细胞、内皮细胞、单核/巨噬细胞、NB样肿瘤细胞、神经元、OC样肿瘤细胞以及OPC样肿瘤细胞。根据内皮细胞差异基因及相应筛选标准,经分析后共筛选出4个基因(DUSP6、STC1、VWA1和TM4SF1)用于风险评分的构建,并经qPCR实验验证目的基因在GBM组织及瘤周正常脑组织中的表达均显著上调。风险评分=0.171*DUSP6+0.144*STC1+0.041*VWA1−0.004*TM4SF1。
    结论 本研究构建的胶质母细胞瘤内皮细胞风险评分能够较好地预测患者预后。

     

    Abstract:
    Objective To explore and verify the prognostic value of endothelial cells in glioblastoma.
    Methods Through bioinformatics analysis of the TCGA and CGGA databases, we screened endothelial cell-related markers in GBM single-cell data according to a series of criteria. Moreover, univariate Cox regression analysis was performed to obtain and screen endothelial cell prognosis-related markers and construct endothelial cell-related prognostic risk score. qPCR experiments was used to verify the differences in the expression of prognostic markers in GBM tissues and peritumoral normal brain tissues. Kaplan-Meier method was used to construct the survival curve to identify the prognostic efficacy of the prognostic risk score.
    Results A total of 2 115 prognostic genes of glioblastoma (GBM) were screened. Among them, 1 494 was upregulated and 621 was downregulated. Seven groups of cells were obtained after GBM single-cell sequencing analysis, including AC-like tumor cells, endothelial cells, monocytes/macrophages, NB-like tumor cells, neurons, OC-like tumor cells, and OPC-like tumor cells. According to the differential genes of endothelial cells and the corresponding screening criteria, four genes (DUSP6, STC1, VWA1, and TM4SF1) were screened for risk-score construction. The expression of the target gene in GBM tissues and normal brain tissues around the tumor was significantly up-regulated detected by qPCR. The risk score=0.171*DUSP6+0.144*STC1+0.041*VWA1−0.004*TM4SF1.
    Conclusion The glioblastoma endothelial cells’ risk score determined in this study can preferably predict the prognosis of patients.

     

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