FBLIM1基因在人脑胶质瘤组织中表达及其生物学功能研究

Bioinformatics analysis of the expression of FBLIM1 gene in human glioma tissue

目的探讨FBLIM1基因在人脑胶质瘤组织中表达、相关生物学功能、信号通路及其与患者预后的相关性.方法癌症基因组图谱数据库(TCGA)中检索FBLIM1在人脑胶质瘤组织中表达情况,分析比较胶质瘤患者肿瘤组织与正常脑组织中FBLIM1 mRNA表达水平是否存在差异.STRING数据库中构建FBLIM1及其相互作用蛋白网络(PPI)同时对网络中的蛋白进行聚类分析.采用基因本体论(GO)和京都基因与基因组百科全书(KEEG)分析网络中相互作用蛋白,预测其可能功能及信号通路.根据FBLIM1基因在胶质瘤中的表达水平中位数分为高和低表达组,绘制生存曲线,比较高低表达组无疾病进展生存(DFS)和总生存(OS)是否存在差异.结果在胶质瘤患者肿瘤组织中FBLIM1基因表达水平显著高于对应的正常脑组织(P<0.05).PPI网络中共有30个相关蛋白,平均蛋白间相互作用关系强度为8.9,局部聚类指数为0.89,呈现明显的聚类表达(P<0.05).采用cytohubb软件进行关键基因筛选(hubb基因),FERMT3、FLNC、VCL、TLN2和TLN1为PPI网络中的关键基因.FBLIM1及其相关蛋白分子功能主要富集于细胞黏附分子结合、肌动蛋白结合、肌动蛋白丝结合、细胞骨架蛋白结合等;KEGG信号通路主要富集于细胞黏附、中枢神经系统肿瘤、细胞增殖、Rap1信号通路、上皮细胞的侵袭、癌症中的蛋白聚糖、白细胞跨内皮迁移等细胞信号通路.根据FBLIM1表达水平中位数,分为高、低表达组,采用Log-rank检验比较高、低表达组患者生存期.胶质瘤总生存(OS)与FBLIM1表达水平无关(HR=1.4,P=0.10),而无疾病进展生存(PFS)在FBLIM1高表达组中显著低于低表达组(HR=1.7,P=0.015).结论FBLIM1在胶质瘤中表达水平明显升高,并且与胶质瘤患者的无疾病进展生存时间有关.

Objective To explore the expression,related biological functions,signaling pathways,and correlation with patient prognosis of FBLIM1 gene in human glioma tissue.Methods Retrieve the expression of FBLIM1 in human glioma tissues from the Cancer Genome Atlas Database(TCGA),and analyze and compare the differences in FBLIM1 mRNA expression levels between tumor tissues of glioma patients and normal brain tissues.Construct FBLIM1 and its interacting protein network(PPI)in the STRING database,and perform cluster analysis on the proteins in the network.Using GO and KEEG to analyze interacting proteins in the network,predict their possible functions and signaling pathways.Divide the median expression level of FBLIM1 gene into high and low expression groups in gliomas,draw survival curves,and compare whether there are differences in disease progression free survival(DFS)and overall survival(OS)between high and low expression groups.Results The expression level of FBLIM1 gene in tumor tissue was significantly higher in glioma patients than in corresponding normal brain tissue(P<0.05).There are a total of 30 related proteins in the PPI network,with an average protein-protein interaction relationship of 8.9 and a local clustering index of 0.89,showing clear clustering expression(P<0.05).Cytohubb software was used for key gene screening(hubb genes),with FERMT3,FLNC,VCL,TLN2,and TLN1 as key genes in the PPI network.FBLIM1 and its related protein molecules are mainly enriched in cell adhesion molecule binding,actin binding,actin filament binding,cytoskeletal protein binding,etc.;the KEGG signaling pathway is mainly enriched in cell adhesion,central nervous system tumors,cell proliferation,Rap1 signaling pathway,epithelial cell invasion,proteoglycans in cancer,white blood cell migration across endothelium,and other cellular signaling pathways.According to the median expression level of FBLIM1,patients were divided into high vs low groups,survival for patients in the high and low expression groups was compared using the Log rank test.The overall survival(OS)of gliomas was not associated with FBLIM1 expression levels(HR=1.4,P=0.10),while PFS was significantly lower in the high FBLIM1 expression group than in the low FBLIM1 expression group(HR=1.7,P=0.015).Conclusion The expression level of FBLIM1 is significantly elevated in glioma and is related to the progression free survival time of glioma patients.