间变脑胶质瘤中异柠檬酸脱氢酶突变对患者术后替莫唑胺化学治疗及预后的影响:285例单中心回顾性研究  

Effect of IDH mutation on postoperative temozolomide chemotherapy and prognosis in anaplastic gliomas:a single-center retrospective study of 285 patients

作　　者：杨沛[1,4] 王宽宇 张传宝 王政[1,4] 游赣[1,4] 单侠[3,4] Yang Pei;Wang Kuanyu;Zhang Chuanbao;Wang Zheng;You Gan;Shan Xia(Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Gamma Knife Treatment Center,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Radiotherapy Center,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Beijing Neurosurgical Institute,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,100070 [2]首都医科大学附属北京天坛医院伽玛刀治疗中心,100070 [3]首都医科大学附属北京天坛医院放疗中心,100070 [4]北京市神经外科研究所,100070

出　　处：《神经疾病与精神卫生》2021年第5期323-331,共9页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金项目(81903060)。

摘　　要：目的分析间变脑胶质瘤中异柠檬酸脱氢酶(IDH)突变与患者临床病理学因素的相关性及对术后化学治疗敏感性的影响。方法回顾性连续纳入中国胶质瘤基因图谱计划(CGGA)数据库中接受开颅手术且术后病理诊断为间变脑胶质瘤(世界卫生组织Ⅲ级)患者,术后接受放射治疗和(或)替莫唑胺(TMZ)化学治疗。肿瘤组织标本在放射治疗和(或)化学治疗前通过手术切除获得,使用QIAamp DNA Mini试剂盒按照说明书从冷冻肿瘤组织中提取基因组DNA,使用纳米滴ND-1000分光光度计测定DNA浓度和质量,进行IDH1/2突变、1p/19q缺失、MGMT启动子甲基化的检测。应用SPSS 16.0软件通过单因素和多因素Cox生存分析分析临床及分子病理因素与患者总生存期的相关性及对术后放射治疗和替莫唑胺化学治疗敏感性的影响;使用GraphpadPrism 8软件进行Kaplan-Meier曲线生存分析。结果共纳入285例间变脑胶质瘤患者,其中201例(70.5%)表现为IDH突变,84例(29.5%)表现为IDH野生。多因素Cox回归分析显示,IDH突变(HR=0.531,95%CI:0.385~0.733,P<0.001)及1p/19q联合缺失(HR=0.352,95%CI:0.179~0.691,P=0.002)均可独立预测患者总生存期,而O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子甲基化的预测价值差异无统计学意义(P=0.071)。IDH突变组中,接受术后TMZ化学治疗的患者较未接受者预后有所改善,但差异无统计学意义(中位生存期:1793 d比1455 d,P=0.059),而在IDH野生组中,TMZ化学治疗对患者预后改善不明显(中位生存期:535 d比415 d,P=0.890)。结论本研究发现IDH突变型间变脑胶质瘤在接受术后TMZ化疗后,预后有改善趋势,相关结果可能为今后WHOⅢ级脑胶质瘤术后化疗的研究提供思路。Objective To analyze the correlation between isocitrate dehydrogenase(IDH)mutation and clinicopathological factors in patients with anaplastic gliomas and its effect on the sensitivity of postoperative chemotherapy.Methods The patients from the Chinese Glioma Genome Atlas(CGGA)database who underwent craniotomy,were pathologically diagnosed as anaplastic glioma(WHO GradeⅢ),and received radiotherapy and/or temozolomide(TMZ)chemotherapy after surgery were retrospectively consecutively included.Tumor tissue samples were obtained by surgical resection before radiotherapy and/or chemotherapy.Genomic DNA was extracted from frozen tumor tissue by QIAamp DNA mini kit according to the instructions.The concentration and quality of DNA were determined by MD-1000 spectrophotometer.IDH1/2 mutation,1p/19q deletion and Mgmt promoter methylation were detected.SPSS 16.0 software was used to analyze the correlation between clinical and molecular pathological factors and overall survival,and the effect on the sensitivity of postoperative radiotherapy and temozolomide chemotherapy.Kaplan-Meier curve survival analysis was performed using GraphpadPrism 8 software.Results A total of 285 patients with anaplastic gliomas were included.Among them,201(70.5%)showed IDH mutation and 84(29.5%)showed IDH wild.Multivariate Cox regression analysis showed that IDH mutation(HR=0.531,95%CI:0.385-0.733,P<0.001)and 1p/19q deletion(HR=0.352,95%CI:0.179-0.691,P=0.002)were both independent predictors of overall survival,while the predictive value of O6 methylguanine DNA methyltransferase(MGMT)promoter methylation had no significant difference(P=0.071).In IDH mutation group,the prognosis of patients receiving TMZ chemotherapy was improved,but the difference was not statistically significant(median survival:1793 d vs 1455 d,P=0.059).In IDH wild group,TMZ chemotherapy did not significantly improve the prognosis(median survival:535 d vs 415 d,P=0.890).Conclusions In this study,it is found that the prognosis of IDH mutant anaplastic glioma after TMZ chemoth

关 键 词：间变脑胶质瘤 异柠檬酸脱氢酶 突变 替莫唑胺 化学治疗 生存预后 

分 类 号：R739.41[医药卫生—肿瘤]