Li Hailong, Li Jiye, Cheng Gang, Zhang Jianning, Li Xuezhen
Department of Neurosurgery, Navy General Hospital, Beijing 100048, China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Clin Neurol Neurosurg. 2016 Dec;151:31-36. doi: 10.1016/j.clineuro.2016.10.004. Epub 2016 Oct 12.
This study aimed to investigate the potential association between IDH mutation and O-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy.
A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis.
Of the 157 GBM patients, 145 (92.36%) patients, including 38 patients with psPD, 38 patients with early progression (ePD), and 69 patients with non-progression (non-PD), were followed up for six to 56 months. We identified a higher rate of MGMT promoter methylation and IDH1 mutation in psPD patients compared with ePD patients (P=0.002). In addition, MGMT promoter methylation and IDH1 mutation predicted a high probability of psPD development in GBM patients (P=0.001 and P<0.001, respectively). MGMT promoter methylation, IDH1 mutation, Karnofsky performance score (KPS) ≥70, and psPD were associated with a significantly longer overall survival of GBM patients (P=0.001, 0.001, 0.002, and P<0.001, respectively). Both of MGMT promoter methylation and IDH mutation had a cumulative effect on the OS of GBM patients. GBM patients with psPD (39.2±2.1months, P<0.001) had a longer median survival (MS) than GBM patients with ePD (11.9±1.1months) or with non-PD (24.4±2.4months).
MGMT promoter methylation and IDH1 mutation were associated with PsPD and predicted a longer median survival in GBM patients after TMZ-based chemoradiotherapy. Genetic analyses of the MGMT promoter and IDH1 may allow us to effectively treat GBM patients.
本研究旨在调查多形性胶质母细胞瘤（GBM）患者在同步进行基于替莫唑胺（TMZ）的放化疗后，异柠檬酸脱氢酶（IDH）突变与O-甲基鸟嘌呤甲基转移酶（MGMT）基因启动子甲基化及假性进展疾病（psPD）之间的潜在关联。
本回顾性研究纳入了157例接受同步基于TMZ放化疗的GBM患者。基于逻辑回归、Cox回归和多变量分析，分析了psPD与包括IDH突变和MGMT启动子甲基化在内的一些人口统计学和遗传因素之间的关联。
157例GBM患者中，145例（92.36%）患者，包括38例psPD患者、38例早期进展（ePD）患者和69例无进展（非PD）患者，接受了6至56个月的随访。我们发现，与ePD患者相比，psPD患者中MGMT启动子甲基化和IDH1突变的发生率更高（P=0.002）。此外，MGMT启动子甲基化和IDH1突变预示GBM患者发生psPD的可能性较高（分别为P=0.001和P<0.001）。MGMT启动子甲基化、IDH1突变、卡诺夫斯基功能状态评分（KPS）≥70以及psPD与GBM患者显著更长的总生存期相关（分别为P=0.001、0.001、0.002和P<0.001）。MGMT启动子甲基化和IDH突变均对GBM患者的总生存期有累积影响。psPD的GBM患者中位生存期（MS）（39.2±2.1个月，P<0.001）比ePD（11.9±1.1个月）或非PD（24.4±2.4个月）的GBM患者更长。
MGMT启动子甲基化和IDH1突变与psPD相关，并预示基于TMZ放化疗后的GBM患者有更长的中位生存期。对MGMT启动子和IDH1进行基因分析可能有助于我们有效治疗GBM患者。
