甲基转移酶样7B在中国人群脑胶质瘤中的表达及预后分析  

Expression and prognostic characteristics of methyltransferase-like 7B in Chinese glioma patients

作　　者：康鹏[1,2] 原林皓 彭嘉宜 王洋洋 贾旺 Kang Peng;Yuan Linhao;Peng Jiayi;Wang Yangyang;Jia Wang(Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,China National Clinical Research Center for Neurological Diseases,Beijing 100070,China;Beijing Neurosurgical Institute,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京天坛医院神经外科,国家神经系统疾病临床医学研究中心,100070 [2]首都医科大学,北京市神经外科研究所,100070

出　　处：《中华神经外科杂志》2020年第6期587-592,共6页Chinese Journal of Neurosurgery

基　　金：北京市医院管理中心"青苗"计划专项经费(QML20180504);北京市优秀人才培养(青年骨干)(2015000021469G221)。

摘　　要：目的探讨甲基转移酶样7B基因(METTL7B)在中国脑胶质瘤患者中的表达特征及其对预后的影响。方法回顾性分析中国脑胶质瘤基因组图谱计划(CGGA)mRNA seq325数据库中表达METTL7B的288例脑胶质瘤患者的测序结果和临床资料,并对肿瘤标本进行免疫组织化学染色。采用Kaplan-Meier生存曲线分析METTL7B的表达水平对不同级别脑胶质瘤患者生存期的影响;采用单因素、多因素Cox回归分析明确影响患者生存期的相关因素。通过Pearson相关性分析筛选METTL7B共表达的基因,应用R软件中的基因富集工具分析基因的生物学功能。结果288例患者中,世界卫生组织(WHO)Ⅱ、Ⅲ、Ⅳ级胶质瘤患者的METTL7B表达量[中位数(四分位数间距)]分别为[1.05(1.93)]、[3.07(3.17)]和[4.71(2.57)];在异柠檬酸脱氢酶1(IDH1)野生型和突变型的胶质瘤中,METTL7B的表达量分别为[4.99(3.40)]和[1.53(2.77)];在无1p/19q共缺失和1p/19q共缺失的胶质瘤中,METTL7B的表达量分别为[3.85(3.39)]和[0.98(1.79)],上述指标比较差异均有统计学意义(均P<0.01)。免疫组织化学染色证实高级别胶质瘤中METTL7B的染色阳性显著高于低级别胶质瘤。METTL7B高表达组和低表达组患者(各144例)的中位生存期分别为20.0个月(1.0~136.0个月)和80.0个月(2.0~149.0个月),差异有统计学意义(P<0.01)。在WHOⅡ~Ⅳ级胶质瘤患者中,METTL7B的高表达量显著降低了患者的生存时间(均P<0.05)。多因素Cox回归分析显示,METTL7B表达量是影响胶质瘤患者生存期的独立影响因素(HR=1.684,95%CI:1.158~2.449,P<0.01)。在CGGA数据库中,与METTL7B表达呈正相关的基因有252个(r>0.45,P<0.05),其生物学功能主要为细胞黏附、碳水化合物代谢和蛋白折叠等,主要参与了内质网中蛋白质加工、局部黏附及癌症中的蛋白聚糖等。结论在脑胶质瘤组织中,随着肿瘤级别的升高,METTL7B的表达量也显著升高,并可作为高级别胶质瘤预后的预测�Objective To examine the expression characteristics of METTL7B in Chinese glioma patients and its role in the patient′s prognosis.Methods We retrospectively reviewed the sequencing results and clinical information of 288 glioma patients with METTL7B expression enrolled in the mRNAseq_325 dataset of Chinese Glioma Genome Atlas(CGGA).Immunohistochemical staining was conducted for the tumor specimens.Kaplan-Meier survival curve was used to study the effect of METTL7B abundance on the survival of patients with varying degrees of gliomas.Univariate and multivariate Cox regression analysis was conducted to identify the factors related to the patient’s survival.The genes co-expressed with METTL7B were screened by Pearson′s correlation analysis,which were subjected to biological function analysis using gene enrichment tool of R software.Results Among 288 patients,the expression level of METTL7B in patients with World Health Organization(WHO)Ⅱ-Ⅳgliomas[median(quartile spacing)]was[1.05(1.93)],[3.07(3.17)]and[4.71(2.57)]respectively,that in IDH1 mutation and IDH1 wildtype was[4.99(3.40)]and[1.53(2.77)]respectively,and that in gliomas with 1p/19q codeletion and 1p/19q non-codeletion tumor tissues was[0.98(1.79)]and[3.85(3.39)]respectively.The results above presented a statistical significance(all P<0.01).Immunohistochemical staining confirmed that METTL7B positive rate was significantly higher in high-grade gliomas than low-grade gliomas.The median survival of METTL7B high and low expression patients(144 cases in each)was 20.0 months(1.0 to 136.0 months)and 80 months(2.0 to 149.0 months),respectively,and the difference was statistically significant(P<0.01).In patients with WHOⅡ-Ⅳgrade gliomas,the high expression of METTL7B significantly reduced the patient′s survival(all P<0.05).Multivariate Cox regression analysis showed that METTL7B expression was the independent influencing factor of the survival of glioma patients(HR=1.684,95%CI:1.158-2.449,P<0.01).In the CGGA database,there are 252 genes positively corr

关 键 词：神经胶质瘤 基因表达 预后 甲基转移酶样7B基因 

分 类 号：R739.41[医药卫生—肿瘤]