Fermitin家族成员1在脑胶质瘤中的表达及其临床意义  

The expression and clinical significance of FERMT1 in gliomas

作　　者：刘玉清[1] 李阳芳[1] 李敬军[1] 韩建立 Liu Yuqing;Li Yangfang;Li Jingjun;Han Jianli(Department of Molecular Neuropathology,Beijing Neurosurgical Institute,Capital Medical University,Beijing 100070,China;Department of Neurosurgery,Gaocheng People's Hospital,Shijiazhuang 052160,China)

机构地区：[1]北京市神经外科研究所分子病理室,100070 [2]石家庄市藁城人民医院神经外科,052160

出　　处：《神经疾病与精神卫生》2021年第5期340-346,共7页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金项目(82003193)。

摘　　要：目的分析Fermitin家族成员1(FERMT1)在脑胶质瘤中的表达特征,并探讨其临床意义及在脑胶质瘤发生发展中的生物学作用。方法纳入中国脑胶质瘤基因组图谱计划(CGGA)mRNA测序数据库中309例样本,按照FERMT1表达量分为高表达组和低表达组,分析其表达特征。将癌症基因组图谱计划(TCGA)mRNA测序数据库的609例样本作为对照,验证FERMT1在脑胶质瘤患者中的表达特征。采用Kaplan-Meier法、Log-rank检验和Cox回归模型评价FERMT1表达与脑胶质瘤患者生存期的关系。通过基因本体(GO)分析和京都基因和基因组百科全书(KEGG)通路富集分析获得FERMT1表达相关基因的功能。结果在CGGA数据库(309例)和TCGA数据库(609例)中,FERMT1在世界卫生组织(WHO)Ⅱ、Ⅲ及Ⅳ级组间表达量的差异均有统计学意义(F值分别为30.08、91.72,均P<0.01),其中Ⅳ级中表达量最低,Ⅱ级中表达量最高;FERMT1在异柠檬酸脱氢酶(IDH)突变型脑胶质瘤中表达水平更高(t值分别为19.87、30.72,均P<0.01);受试者工作特征(ROC)曲线显示,FERMT1表达量可以很好地预测IDH突变型脑胶质瘤,其曲线下面积(AUC)分别为92.7%和94.8%;FERMT1在四分型组间表达量的差异均有统计学意义(F值分别为94.04、300.20,均P<0.01),其中在前神经元型中表达最高;FERMT1在O6-甲基鸟嘌呤甲基转移酶(MGMT)启动子甲基化组的表达量更高,差异有统计学意义(t值分别为6.65、13.41,均P<0.01);在CGGA和TCGA数据库中,FERMT1低表达组患者较高表达组生存期短(P<0.01);单因素和多因素Cox回归分析结果显示,FERMT1表达水平和病理级别为影响胶质母细胞瘤患者预后的独立危险因素(RR=0.718,95%CI:0.517~0.996,P=0.047;RR=2.519,95%CI:1.763~3.599,P<0.001)。GO富集分析显示,与FERMT1负相关的基因可能与脑胶质瘤的细胞黏附、细胞外基质组成、炎性反应、白细胞迁移和趋化作用等生物学过程有关。KEGG通路富集分析显示,与FERMT1负相关�Objective To determine the expression profile of FERMT1 in gliomas,and to explore the clinical significance and its biological processes involved in the development and progression of gliomas.Methods Clinical data and RNA sequencing expression data from 309 glioma patients was obtained from the Chinese Glioma Genome Atlas(CGGA)database.According to FERMT1 expression,they were divided into high expression group and low expression group,and the expression characteristics were analyzed.While 609 samples from the Cancer Genome Atlas(TCGA)mRNA sequencing database were used as controls to verify the expression characteristics of FERMT1 in glioma patients.Kaplan Meier method,Log-rank test and Cox regression model were used to evaluate the relationship between FERMT1 expression and the survival of glioma patients.Gene oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed for the functional analysis of FERMT1.Results In the CGGA(309 cases)and TCGA datasets(609 cases),the expression of FERMT1 was distinct from WHOⅡ,ⅢandⅣgrade with statistical significance(F=30.08,91.72,respectively,P<0.01),with the lowest expression in WHOⅡgrade and the highest in WHOⅣgrade.FERMT1 expression is higher in isocitrate dehydrogenase(IDH)mutant gliomas(t=19.87,30.72,respectively,P<0.01).The receiver operating characteristic(ROC)curve showed that FERMT1 expression could well predict IDH mutant gliomas,and the area under the curve(AUC)were 92.7%and 94.8%,respectively.In the two cohorts,there were significant differences in FERMT1 expression in different subtypes(F=94.04,300.20,P<0.01),with the highest expression level in proneural subtype.The expression of FERMT1 was higher in the methylation group of O6 methylguanine methyltransferase(MGMT)promoter,and the difference was statistically significant(t=6.65,13.41,respectively,P<0.01).The patients with high expression of FERMT1 had dramatically shorter overall survival than low-expression counterparts in CGGA and TCGA RNAseq databases(P<0.01).The results of single fact

关 键 词：胶质瘤 预后 生存期 Fermitin家族成员1 

分 类 号：R739.41[医药卫生—肿瘤]