钙腔蛋白基因在脑胶质瘤中的表达及其临床意义  

Expression and clinical significance of calumenin in brain gliomas

作　　者：康鹏[1,2] 张传宝 原林皓[1] 彭嘉宜 王洋洋 贾旺 钱珂 Kang Peng;Zhang Chuanbao;Yuan Linhao;Peng Jiayi;Wang Yangyang;Jia Wang;Qian Ke(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 Uniersity,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2期130-135,共6页Chinese Journal of Neurosurgery

基　　金：北京市医院管理局"青苗"计划(QML20180504);北京市优秀人才培养计划(2015000021469G221)。

摘　　要：目的检测钙腔蛋白(CALU)基因在脑胶质瘤中的表达,探讨CALU对脑胶质瘤患者预后的影响,分析CALU共表达基因的相关生物学功能。方法回顾性分析中国脑胶质瘤基因组图谱计划(CGGA)mRNAseq_325数据库中CALU阳性表达的288例脑胶质瘤患者的CALU测序表达量和临床资料,分析不同类型脑胶质瘤患者CALU的表达水平对生存期的影响,采用多因素Cox回归法分析影响患者生存期的相关因素。采用Pearson相关性分析筛选与CALU共表达的相关基因,应用在线富集分析工具分析共表达基因的生物学功能。结果288例患者中,世界卫生组织(WHO)Ⅱ、Ⅲ、Ⅳ级患者CALU的表达量分别为4.74±0.68、5.49±1.12及6.17±0.94;异柠檬酸脱氢酶l(IDH1)野生型和突变型的脑胶质瘤中,CALU的表达量分别为6.13±1.17、5.08±0.76;无1p/19q共缺失和有1p/19q共缺失的胶质瘤中,CALU的表达量分别为5.79±0.07、4.71±0.07。上述指标比较,差异均有统计学意义(均P<0.01)。不同性别间、原发与复发性胶质瘤患者CALU的表达量差异均无统计学意义(均P>0.05)。CALU高表达、低表达患者(各144例)的中位生存期分别为13.0(1~132)个月和82.5(2~149)个月,差异有统计学意义(P<0.01)。在WHOⅡ~Ⅳ级胶质瘤患者中,CALU的高表达量主要与Ⅲ、Ⅳ级患者的生存时间降低有关(均P<0.01)。多因素Cox回归分析显示,CALU表达量是胶质瘤患者生存期的独立影响因素(RR=2.193,95%CI:1.507~3.192,P<0.01)。CGGA数据库中,与CALU表达呈正相关的基因有325个,这些基因的生物学功能主要为信号传导、细胞黏附及细胞代谢等,主要参与了内质网内的蛋白质处理、黏附作用及癌症通路。结论CALU与脑胶质瘤的恶性程度相关,其可作为高级别胶质瘤患者预后的预测因子,以及潜在的研究和治疗靶点。Objective To detect the expression of calumenin(CALU)in human brain glioma samples,to explore its effect on the patient′s outcome,and to analyze the related biological functions of the genes co-expressed with CALU.Methods A retrospective analysis was conducted on CALU sequencing expression and clinical data of 288 glioma patients with positive CALU expression in the mRNAseq_325 database of Chinese Glioma Genome Atlas(CGGA).We analyzed the effects of CALU expression levels on survival in different types of glioma patients.The multivariate Cox regression method was used to determine the relevant factors affecting the survival of glioma patients.Pearson correlation analysis was employed to screen the related genes co-expressed with CALU and their biological functions were explored using the online bioinformatic analysis tools.Results Among the 288 patients,the expression of CALU was 4.74±0.68,5.49±1.12 and 6.17±0.94 in World Health Organization(WHO)gradeⅡ,Ⅲ,andⅣpatients respectively,and 6.13±1.17 and 5.08±0.76 in isocitrate dehydrogenase l(IDH1)wild-type and IDH1 mutant gliomas respectively,and 5.79±0.07 and 4.71±0.07 in gliomas with 1p/19q non-codeletion and 1p/19q co-deletion.The comparative differences in the above indicators were statistically significant(all P<0.01).There was no statistically significant difference in the expression of CALU between males and females or between primary and recurrent gliomas(both P>0.05).The median survival of CALU patients with high and low expression levels(144 cases in each)was 13.0(1-132)months and 82.5(2-149)months,respectively,which had statistically significant difference(P<0.01).In patients with WHO gradeⅡ-Ⅳgliomas,the high expression of CALU mainly reduced the survival time of gradeⅢandⅣpatients(both P<0.01).The multivariate Cox regression analysis showed that CALU expression was an independent factor influencing the survival of glioma patients(RR=2.193,95%CI:1.507-3.192,P<0.01).In the CGGA database,there were 325 genes that were positively correla

关 键 词：神经胶质瘤 基因表达 预后 钙腔蛋白 

分 类 号：R73[医药卫生—肿瘤]