GZMA是IDH突变型神经胶质瘤的预后生物标志物且与免疫浸润相关
GZMA--a prognostic biomarker for IDH mutant glioma and a correlator with immune infiltration
强亦龙 1马晨雨 2张研宇 2林伟2
作者信息
- 1. 西安医学院研究生工作部,陕西 西安 710021;空军军医大学西京医院神经外科,陕西 西安 710032
- 2. 空军军医大学西京医院神经外科,陕西 西安 710032
- 折叠
摘要
目的 探讨颗粒酶A(Granzyme A,GZMA)在脑胶质瘤中的预后价值及其与免疫细胞浸润的相关性.方法 使用生物信息学(R语言)对CGGA数据库中胶质瘤转录组数据集中的低级别胶质瘤(LGG,WHO Grade Ⅱ,IDH-Mutant)和高级别胶质瘤(HGG,WHO Grade Ⅳ,IDH-Mutant)两组数据进行差异基因表达分析.使用R软件包对上调基因集做GO/KEGG富集分析.使用TIMER、GEPIA网络平台和TCGA数据集分析了GZMA表达与神经胶质瘤免疫浸润之间的关系.同时评估了GZMA对神经胶质瘤患者生存的影响.结果 GZMA在IDH突变型HGG中上调(P<0.05),基因集富集分析结果显示GZMA参与了几个顶级且显著富集的GO类别.与正常脑组织相比,GZMA的mRNA在神经胶质瘤样本中均上调(P<0.05),并与神经胶质瘤患者的预后和分级相关.Kaplan-Meier(K-M)曲线分析显示,GZMA高表达的患者比GZMA低表达的患者总生存期(OS)更短.此外,GZMA的表达可能影响神经胶质瘤的免疫浸润水平.在GBM中,GZMA的表达水平与B细胞、树突状细胞的表达水平呈正相关,而与CD8+T细胞、CD4+T细胞的表达水平呈负相关;在LGG中,GZMA的表达水平与各种免疫细胞的浸润均呈正相关(P<0.05).结论 GZMA可作为判断胶质瘤预后和免疫细胞侵袭的候选生物标志物.
Abstract
Objective To explore the prognostic value of Granzyme A(GZMA)in gliomas and its correlation with immune cell infiltration.Methods Differential gene expressions correlative with the two sets of data from low-grade glioma(LGG,WHO GradeⅡ,IDH Mutant)and high-grade glioma(HGG,WHO Grade Ⅳ,IDH Mutant)in the glioma transcriptome dataset of CGGA database were analyzed by bioinformatics tool(R language).The GO/KEGG enrichment analysis of the upregulated gene set was carried out by using R software package.The relationship between GZMA expression and Glioma immune infiltration was analyzed through network platforms including TIMER and GEPIA as well as TCGA data sets.Simultaneously,effects of GZMA on the survival span of the neuroglioma patients were evaluated.Results The expression level of GZMA was upregulated in IDH-mutant high-grade gliomas.Outcomes of gene set enrichment analysis showed that GZMA was involved in several top and significantly enriched GO categories.Compared to normal brain tissue,mRNA expression levels of GZMA in all the glioma samples were upregulated and relevant to both prognosis and classification of glioma patients.Kaplan Meier(K-M)survival curve analysis indicated that patients with high GZMA expression had shorter overall survival(OS)time than those with low GZMA expression.Moreover,the expression level of GZMA might affect the immune infiltration level in gliomas.The expression level of GZMA in GBM was positively correlated with expression levels of both B cells and dendritic cells,while negatively associated with expression levels of CD8+T cells and CD4+T cells.In contrast to GBM,the expression level of GZMA was positively correlated with infiltration levels of various immune cells.Conclusion GZMA can function as a potential biomarker in the judgment of prognosis and immune cell invasion in glioma.
关键词
胶质细胞瘤/免疫浸润/颗粒酶AKey words
Glioma/Immune cell infiltration/Granzyme A引用本文复制引用
基金项目
国家自然科学基金项目(82303425)
陕西省自然科学基础研究计划重点项目(2021JZ-34)
出版年
2024
NETL
NSTL
万方数据