NOG基因作为潜在生物标志物在脑胶质瘤中的表达和临床意义  

The expression and clinical significance of NOG as a potential biomarker in glioma

作　　者：杨桂涛 赵北川 凌耿强 YANG Guitao;ZHAO Beichuan;LING Gengqiang(Neuro-Medicine Center,the Seventh Affiliated Hospital of Sun-Yat-sen University,Guangdong Shenzhen 518107,China;Department of Neurosurgery,the First Affiliated Hospital of Sun-Yat-sen University,Guangdong Guangzhou 510080,China)

机构地区：[1]中山大学附属第七医院神经医学中心,广东深圳518107 [2]中山大学附属第一医院神经外科,广东广州510080

出　　处：《现代肿瘤医学》2023年第23期4344-4350,共7页Journal of Modern Oncology

基　　金：广东省深圳市科技计划基础研究(面上项目)(编号:JCYJ20190809151007769)。

摘　　要：目的:基于生物信息学分析NOG基因在胶质瘤中的表达和预后价值,并推断NOG对胶质瘤发生发展的生物学功能。方法:从CGGA和TCGA数据库分别下载并筛选后得到422例和702例胶质瘤的mRNA表达数据集和临床信息数据集,采用非参数秩和检验分析NOG的差异表达情况。采用Kaplan-Meier生存曲线法和Cox分析法分析NOG对胶质瘤预后的预测价值。将CGGA和TCGA数据库中NOG与其他基因进行相关分析,筛选出强相关基因后,进行GO和KEGG分析。将NOG与血管生成相关基因集(angiogenesis related gene set,ARGS)进行GSVA分析,与血管生成拟态(vasculogenic mimicry,VM)相关基因进行相关分析。结果:成人胶质瘤WHO分级较低,年龄较小,则NOG表达量较高(P<0.001)。NOG在IDH突变型、1p19q共缺失、MGMT甲基化的组别中显著高表达(P<0.001)。生存分析显示,NOG高表达组的OS显著高于低表达组(P<0.0001)。Cox回归分析显示,TCGA数据中NOG表达水平是OS的独立预后因素[HR=0.395,95%CI(0.236,0.662)]。GO和KEGG分析显示,NOG富集在神经系统发育、成骨细胞分化、血管生成、细胞黏附、整合素、黏着斑、细胞外基质结构、TGF-β信号通路和肿瘤的蛋白聚糖等。GSVA分析提示,NOG表达与血管生成呈负相关关系。相关分析表明,NOG表达与胶质瘤VM相关基因表达呈负相关关系。结论:NOG基因在胶质瘤中存在差异表达,与分子标志物关系密切,是OS的独立预后因素,NOG高表达提示预后良好。NOG可能与神经系统发育、骨骼系统发育、血管生成、细胞迁移、TGF-β信号通路和肿瘤细胞的迁移、侵袭、转移关系密切。NOG可能参与胶质瘤内皮依赖性血管生成的负调控,同时抑制血管生成拟态形成。NOG在胶质瘤发生发展中可能起抗肿瘤作用,可作为胶质瘤的预后指标和潜在的靶向治疗生物标志物。Objective:To analyze the expression and prognostic value of NOG in gliomas based on bioinformatics and inferring the biological function of NOG in the occurrence and development of gliomas.Methods:After downloading and screening the data from CGGA and TCGA databases,mRNA expression datasets and clinical information datasets of 422 and 702 glioma cases were obtained.Non parametric rank sum test was used to analyze the differential expression of NOG.The predictive value of NOG for glioma prognosis was analyzed using Kaplan-Meier survival curve and Cox analysis.Performed correlation analysis between NOG and other genes in CGGA or TCGA databases,screened out strongly correlated genes,and performed GO and KEGG analysis.GSVA between NOG and ARGS were conducted.Correlation analysis between NOG and VMRG were conducted.Results:Adult gliomas with lower WHO grading and younger age have higher levels of NOG expression(P<0.001).NOG is significantly overexpressed in the IDH mutant,1p19q codeletion,and MGMT methylation groups(P<0.001).Survival analysis shows that the OS of the NOG high expression group is significantly higher than that of the low expression group(P<0.0001).Cox regression analysis shows that the expression level of NOG in TCGA is an independent prognostic factor for OS[HR=0.395,95%CI(0.236,0.662)].GO and KEGG analysis shows that NOG is enriched in nervous system development,osteoblast differentiation,angiogenesis,cell adhesion,integrins,adhesive plaques,extracellular matrix structure,and TGF-βsignal pathways and tumor proteoglycans.GSVA analysis shows the expression of NOG is negatively correlated with angiogenesis.Correlation analysis shows the expression of NOG was negatively correlated with the expression of VM related genes in glioma.Conclusion:There is differential expression of NOG in gliomas,which is closely related to molecular markers and is an independent prognostic factor for OS.High expression of NOG suggests a good prognosis.NOG may be associated closely with nervous system development,skeletal sys

关 键 词：生物信息学 胶质瘤 NOG 预后 生物标志物 

分 类 号：R739.41[医药卫生—肿瘤]