人低级别胶质瘤IDH1基因突变与临床病理参数的关系

Relationship between IDH1 mutation and clinicopathological parameters in human low-grade gliomas

目的通过对人低级别胶质瘤异柠檬酸脱氢酶1(IDH1)基因突变检测,探讨IDH1突变与临床病理参数及预后的关系。方法收集143例低级别胶质瘤(WHOⅡ级94例、WHOⅢ级49例)患者的石蜡组织标本进行DNA提取,经聚合酶链反应扩增后用Sanger测序法对IDH1基因第132位密码子进行突变检测,同时分析患者性别、年龄、肿瘤位置及最大径、组织学类型及WHO分级、无进展生存期(PFS)等临床病理参数与IDH1突变的关系。结果143例低级别胶质瘤患者中,检测出IDH1基因R132突变型118例,野生型25例,突变率为82.52%。IDH1基因R132突变与较低年龄(P<0.001)、肿瘤组织学分型(P=0.018)、WHOⅡ级(P=0.03)、Ki-67指数较低(P=0.018)、随访期间无复发(P<0.001)呈正相关。生存分析Kaplan-Meier生存曲线显示,IDH1基因突变对患者预后有影响(χ^2=14.948,P<0.001),Cox回归多因素分析显示,IDH1基因突变和WHO分级具有统计学意义(P均<0.001),而肿瘤位置、最大径、肿瘤是否全切除、术后有无辅助治疗、Ki-67指数等因素差异无统计学意义。结论低级别胶质瘤IDH1基因突变率为82.52%,IDH1突变与年龄、肿瘤组织学分型、WHO分级、Ki-67指数及有无复发相关,IDH1突变型低级别胶质瘤比IDH1野生型预后相对较好,可作为判断胶质瘤患者预后的指标并为胶质瘤治疗提供潜在靶点。

Objective To investigate the relationship between isocitrate dehydrogenase 1(IDH1)gene mutation and clinicopathological parameters and prognosis by detecting IDH1 mutation in low-grade gliomas.Methods The paraffin tissue samples of 143 cases of low-grade glioma(WHOⅡ94 cases,WHOⅢ49 cases)were collected for DNA extraction.The mutation at codon 132 of IDH1 gene was detected by Sanger sequencing after polymerase chain reaction(PCR)amplification.Meanwhile,multiple-factor analysis was used on patients'sex,age,tumor location and maximum diameter,histological type,WHO grade and Progression-Free Survival(PFS)to investigate the correlations of IDH1 mutation and clinicopathological parameters and prognostic value.Results A total of 118 IDH1 gene R132 mutations among the 143 cases(82.52%)were detected out.R132 mutation of IDH1 gene was correlated with age(P<0.001),tumor histological classification(P=0.018),WHOⅡ(P=0.03),lower Ki-67 index(P=0.018),no recurrence during follow-up(P<0.001).Survival analysis in the Kaplan-Meier survival curve showed that IDH1 gene mutation had an effect on the prognosis of patients(χ2=14.948,P<0.001).Cox regression multivariate analysis showed that IDH1 gene mutation and WHO grade were statistically significant(P<0.001),while the location,maximum diameter,total resection of tumor,postoperative adjuvant therapy,Ki-67 index and other factors had no statistical significance.Conclusion The mutation rate of IDH1 gene in low-grade gliomas was 82.52%.IDH1 mutation was associated with age,histological type,WHO grade,Ki-67 index and recurrence.IDH1 mutation presented notable effect on the prognosis of glioma patients,It can be used as a prognostic index and provide a potential target for the treatment of gliomas.