基于生物信息学分析胶质母细胞瘤中RUNX1基因的表达及临床意义  

Analysis of RUNX 1 gene expression and clinical significance in glioblastoma based on bioinformatics

作　　者：陈亚伦 宋彦[1] CHEN Yalun;SONG Yan(Department of Neurology,Nanyang Second People's Hospital,Nanyang,Henan 473012,China)

机构地区：[1]南阳市第二人民医院神经内科,河南南阳473012

出　　处：《现代医药卫生》2022年第13期2165-2171,共7页Journal of Modern Medicine & Health

基　　金：河南省卫生健康委员会医学科技攻关计划联合共建项目(LHGJ20191467)。

摘　　要：目的通过高通量的肿瘤生物学信息数据库,分析Runt相关转录因子1(RUNX1)在胶质母细胞瘤(GBM)中的表达和预后关系,以及初步的分子机制。方法检索GEO数据库,利用GEO2R工具分析GBM相关的三组基因芯片(GSE50161、GSE108476和GSE15824),筛选显著高表达的差异基因。运用TCGA数据库分析工具:GEPIA在线工具分析RUNX1和补体调节因子Ⅰ(CFⅠ)在GBM中的表达及和临床预后的关系,同时分析RUNX1与CFⅠ等基因表达的相关性。运用JASPAR转录因子数据库分析RUNX1与CFⅠ的转录调控关系。然后采用TISCH单细胞测序数据库分析RUNX1在肿瘤微环境中的表达情况。最后运用GeneMANIA数据库分析RUNX1的蛋白相互作用网络和可能参与调控的信号通路,并通过siRNA细胞干扰实验和增殖实验进行初步验证。结果通过分析三组基因芯片发现RUNX1和CFⅠ在GBM中显著高表达,且GEPIA工具分析显示GBM组RUNX1和CFⅠ表达明显高于正常组,差异均有统计学意义(P<0.05)。RUNXI和CFⅠ基因对肿瘤患者的生存预后有显著相关性(相关系数=0.6,P<0.05)。转录因子数据分析发现RUNX1可能在转录水平调控CFⅠ的表达。单细胞数据库分析发现RUNX1在肿瘤细胞及免疫细胞中均异常高表达。蛋白质相互作用网络分析发现RUNX1被干扰后,Wnt通路的下游分子β-catenin及下游靶基因MYC和CD44的mRNA水平也明显下调,RUNX1下调明显抑制了肿瘤细胞的增殖。结论RUNX1在GBM中高表达,且提示临床预后不良。初步的分子机制提示RUNX1可能通过转录调节CFⅠ的表达抑制免疫反应,同时通过激活Wnt/β-catenin信号促进肿瘤的发生、发展。Objective To analyze the relationship between the expression of Runt-related transcription factor 1(RUNX 1)and prognosis in glioblastoma(GBM),explore the preliminary molecular mechanism,through a high-throughput database of tumor biology information.Methods The Gene Expression Omnibus(GEO)database was searched,and three groups of GBM-related gene chips(GSE50161,GSE108476 and GSE15824)were analyzed and the differentially expressed genes was screened by GEO2R tool.By using TCGA database analysis tool:the expression of RUNX1 and complement factor Ⅰ(CFⅠ)in glioblastoma and their relationships with clinical prognosis were analyzed by GEPIA online tool,and the correlation between RUNX1 and CFⅠ gene expression was also analyzed.The JASPAR transcription factor database was used to analyze the transcriptional regulatory relationship between RUNX1 and CFⅠ.Then the expression of RUNX1 in the tumor microenvironment was analyzed by TISCH single cell sequencing database.Finally,the protein-protein interaction network of RUNX1 and the possible signal pathways involved in regulation were analyzed by GeneMANIA database,and the siRNA cell interference experiment and proliferation experiment were performed for preliminary validation.Results By analyzing three groups of gene chips,it was found that RUNX1 and CFⅠ were significantly high expression in glioblastoma,and GEPIA tool analysis showed that the expression of RUNX1 and CFⅠ in GBM group was significantly higher than that in normal group,and the difference was statistically significant(P<0.05).RUNXI and CFⅠ genes were significantly correlated with the survival and prognosis of tumor patients(correlation coefficient=0.6,P<0.05).Analysis of transcription factor data found that RUNX1 may regulate CFⅠ expression at the transcriptional level.The single-cell database analysis found that RUNX1 was abnormally highly expressed in tumor and immune cells.Protein interaction network analysis indicated that after RUNX1 was disturbed,the downstream molecule β-catenin and the

关 键 词：数据库分析 Runt相关转录因子1 补体调节因子Ⅰ 胶质母细胞瘤 

分 类 号：R739.41[医药卫生—肿瘤]