豆甾醇治疗胶质母细胞瘤靶基因预测及相关预后模型的建立  

Prediction of target genes and establishment of related prognostic model for the treatment of glioblastoma with stigmasterol

作　　者：朱强 李瑞春[1] 郭世文[1] 梁晨[1] ZHU Qiang;LI Ruichun;GUO Shiwen;LIANG Chen(Department of Neurosurgery,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Department of Neurosurgery,the Affiliated Hospital of Yan’an University,Yan’an 716000,China)

机构地区：[1]西安交通大学第一附属医院神经外科,陕西西安710061 [2]延安大学附属医院神经外科,陕西延安716000

出　　处：《西安交通大学学报（医学版）》2024年第6期909-917,共9页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省重点研发计划项目(No.2024SF-YBXM-047)。

摘　　要：目的 预测豆甾醇治疗胶质母细胞瘤(glioblastoma, GBM)的潜在靶基因并构建相关预后模型,以期揭示其抗胶质瘤的作用机制,并探讨这些靶基因在GBM患者预后中的作用。方法 通过数据库获得GBM差异表达基因及豆甾醇靶基因,使用韦恩图筛选豆甾醇治疗GBM的潜在靶基因并使用R语言进行富集分析。采用单因素COX回归分析和最小绝对收缩与选择算子(least absolute shrinkage and selection operator, LASSO)分析筛选与GBM患者预后相关的豆甾醇靶基因并构建相关的预后模型。采用逆转录实时荧光定量聚合酶链反应(real-time quantitative reverse transcription polymerase chain reaction, RT-qPCR)和Western blotting分析检测豆甾醇对相关靶基因表达的影响。结果 共获得31个豆甾醇治疗GBM的潜在靶基因。富集分析显示,这些靶基因与G蛋白偶联受体(G protein-coupled receptor, GPCR)信号通路的激活和脂质代谢的调控有关。回归分析筛选出2个与GBM预后相关的豆甾醇靶基因脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)和α-1B肾上腺素能受体(alpha-1B adrenergic receptor, ADRA1B),基于这2个基因构建的预后模型能够准确预测GBM患者的预后。豆甾醇能够抑制GBM细胞中这2种基因在转录及翻译水平的表达(FABP5:t=9.909,P=0.001;ADRA1B:t=3.319,P=0.029)。结论 豆甾醇的抗胶质瘤作用可能与GPCR信号通路及脂质代谢的调控有关。通过抑制FABP5及ADRA1B的表达,豆甾醇可能具有改善GBM患者预后的潜在作用。同时,以FABP5及ADRA1B的表达水平构建的预后模型在预测GBM患者预后及监测疗效方面可能能够发挥一定的作用。Objective To predict potential target genes for the treatment of glioblastoma(GBM)with stigmasterol and construct a relevant prognostic model,in order to reveal its antiglioma mechanism and the role of these target genes in the prognosis of GBM patients.Methods Differential expression genes in GBM and stigmasterol target genes were obtained via online databases.Venn diagram was used to select potential target genes for stigmasterol treatment of GBM,and enrichment analysis was performed using R language.Univariate COX regression analysis and least absolute shrinkage and selection operator(LASSO)analysis were made to select stigmasterol target genes related to the prognosis of GBM patients and construct a relevant prognostic model.Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blotting analyses were used to detect the effect of stigmasterol on the expressions of related target genes.Results In this study,a total of 31 potential target genes for the treatment of GBM with stigmasterol were identified.Enrichment analysis showed that these target genes were associated with the activation of the G protein coupled receptor(GPCR)signaling pathway and the regulation of lipid metabolism.Regression analysis identified two stigmasterol target genes,namely,fatty acid binding protein 5(FABP5)and alpha 1B adrenergic receptor(ADRA1B),which are associated with the prognosis of GBM.A prognostic model constructed based on these two genes could accurately predict the prognosis of GBM patients.Finally,stigmasterol inhibited the expressions of these two genes in GBM cells(FABP5:t=9.909,P=0.001;ADRA1B:t=3.319,P=0.029).Conclusion Stigmasterol’s anti-tumor effect may be linked to its regulation of GPCR signaling pathways and lipid metabolism.By inhibiting the expressions of FABP5 and ADRA1B,stigmasterol could potentially enhance the prognosis for GBM patients.Additionally,a prognostic model based on the expression levels of FABP5 and ADRA1B can be valuable for predicting patient outcomes and m

关 键 词：豆甾醇 胶质母细胞瘤(GBM) 预后模型 

分 类 号：R730.5[医药卫生—肿瘤]