ITGA3在脑胶质瘤中的表达及其对预后的评估价值  

Integrin alpha 3 expression in glioma and its prognostic value in glioma patients

作　　者：周祥[1] 王仲伟[1] 常海刚[1] 赵树鹏[1] 金保哲[1] Zhou Xiang;Wang Zhongwei;Chang Haigang;Zhao Shupeng;Jin Baozhe(Department of Neurosurgery,First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,China)

机构地区：[1]新乡医学院第一附属医院神经外科,卫辉453100

出　　处：《中华神经医学杂志》2022年第3期232-241,共10页Chinese Journal of Neuromedicine

摘　　要：目的分析整合素α3(ITGA3)mRNA和蛋白在不同级别、临床及分子特征脑胶质瘤组织、细胞系之间表达的差异,探讨其对脑胶质瘤患者预后的评估价值。方法(1)分别从癌症基因组图谱(TCGA)数据库和中国脑胶质瘤图谱(CGGA)数据库提取脑胶质瘤ITGA3 mRNA的表达数据和患者的临床资料。比较不同世界卫生组织(WHO)分级、年龄、性别、异柠檬酸脱氢酶(IDH)突变状态、染色体1p/19q缺失状态脑胶质瘤间ITGA3 mRNA表达的差异。采用Kaplan-Meier法绘制并比较ITGA3 mRNA高表达组、ITGA3 mRNA低表达组患者的生存曲线。受试者工作特征(ROC)曲线分析ITGA3 mRNA对患者生存率的预测效能。单因素和多因素Cox回归分析明确患者预后的独立影响因素。将预后的独立影响因素构建列线图,应用校准图来验证列线图预测患者预后的可靠性。(2)通过人类蛋白质图谱(HPA)在线数据库测定ITGA3的细胞内定位和低、高级别脑胶质瘤中ITGA3蛋白表达。(3)体外培养脑胶质瘤细胞U87、U118、U251和人星形胶质细胞SVG,采用Western blotting、RT-PCR分别检测各细胞中ITGA3 mRNA和蛋白的表达。结果(1)TCGA数据库中,WHO分级Ⅱ、Ⅲ级、Ⅳ级胶质瘤ITGA3 mRNA的表达依次增加,差异有统计学意义(P<0.05)。CGGA数据库中,WHO分级Ⅳ级胶质瘤ITGA3 mRNA的表达高于Ⅱ级、Ⅲ级胶质瘤,差异有统计学意义(P<0.05)。TCGA和CGGA数据库中,≤40岁和>40岁、IDH野生型和IDH突变型、染色体1p/19q缺失和无缺失患者间胶质瘤ITGA3 mRNA表达的差异均有统计学意义(P<0.05)。无论是总体胶质瘤,还是低级别胶质瘤和胶质母细胞瘤中,ITGA3 mRNA低表达组患者的生存率均高于ITGA3 mRNA高表达组,差异均有统计学意义(P<0.05)。ROC曲线分析显示:TCGA数据库中ITGA3 mRNA预测脑胶质瘤患者1、3、5年生存率的曲线下面积(AUC)分别为0.791、0.786、0.708。CGGA数据库中ITGA3 mRNA预测脑胶质瘤患者1、3、5年生存�Objective To investigate the differences of integral alpha 3(ITGA3)mRNA and protein expressions in gliomas of different grades and different cell lines,and gliomas tissues of different clinical and molecular characteristics,and evaluate their prognostic values in brain glioma patients.Methods(1)ITGA3 mRNA expression data in the brain gliomas and clinical data of these glioma patients were obtained from The Cancer Genome Atlas(TCGA)and Chinese Glioma Genome Atlas(CGGA).The differences of ITGA3 mRNA expressions in glioma patients with different gender,ages,WHO grading,isocitrate dehydrogenase 1(IDH)mutation statuses,and 1p/19q co-deletion statuses were compared.Kaplan-Meier method was used to plot and compare the survival curves of patients with ITGA3 mRNA high expression and ITGA3 mRNA low expression.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficiency of ITGA3 mRNA expression in survival rate of gliomas.Univariate and multivariate Cox regression analyses were used to explore the independent influencing factors for prognoses in glioma patients.The independent influencing factors for prognosis were used to construct nomograms and the calibration diagram was used to verify the reliability of nomograms in predicting the prognoses of these patients.(2)Intracellular localization of ITGA3 and ITGA3 protein expression in low-and high-grade gliomas were determined by on-line database of Human Protein Atlas(HPA).(3)Brain glioma cells U87,U118,U251 and human astrocytes SVG were cultured in vitro,and the ITGA3 mRNA and protein expressions in cells were detected by Western blotting and reverse transcription(RT)-PCR,respectively.Results(1)In TCGA database,the ITGA3 mRNA expressions in gliomas of WHO grading II,III and IV increased successively,with significant differences(P<0.05).In CGGA database,the ITGA3 mRNA expression in glioma of WHO grading IV was statistically higher than that in glioma of WHO grading II and III(P<0.05).In TCGA and CGGA databases,the ITGA3 mRNA expressions in glioma

关 键 词：神经胶质瘤 整合素Α3 差异表达 预后 

分 类 号：R739.41[医药卫生—肿瘤]