2-羟基戊二酸联合谷氨酸及谷氨酰胺无创预测低级别胶质瘤异柠檬酸脱氢酶基因突变状态的磁共振波谱研究  

MR spectroscopy for noninvasive prediction of IDH status in low-grade glioma with 2-hydroxyglutarate integrated with glutamate and glutamine

作　　者：俞梅美 沈慧聪[1] 常天静 葛颖 王子璇 陈绪珠[1] 季楠[3] 厉欣 再帕尔·阿不力孜 Yu Meimei;Shen Huicong;Chang Tianjing;Ge Ying;Wang Zixuan;Chen Xuzhu;Ji Nan;Li Xin;Abliz Zeper(Department of Radiology,Beijing Tiantan Hospital Affiliated to Capital Medical University,Beijing 100070,China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Department of Neurosurgery,Beijing Tiantan Hospital Affiliated to Capital Medical University,Beijing 100070,China;Center for Imaging and Systems Biology,Minzu University of China,Beijing 100081,China)

机构地区：[1]首都医科大学附属北京天坛医院放射科,100070 [2]天然药物活性物质与功能国家重点实验室中国医学科学院北京协和医学院药物研究所,100050 [3]首都医科大学附属北京天坛医院神经外科,100070 [4]中央民族大学生物成像与系统生物学研究中心,北京100081

出　　处：《中华放射学杂志》2021年第8期823-828,共6页Chinese Journal of Radiology

基　　金：NSFC国家重大科研仪器研制项目(21927808);北京高校高精尖学科建设项目;国家自然科学基金项目(81772005)。

摘　　要：目的采用长TE单体素不对称自旋回波点解析波谱(PRESS)成像探讨临床中有效判别异柠檬酸脱氢酶(IDH)基因突变状态的功能影像学指标。方法前瞻性纳入术前拟诊为低级别胶质瘤的患者25例,并根据病理结果分为IDH基因突变组和IDH基因野生组。所有患者均接受长TE PRESS MRS扫描。患者的IDH基因突变状态均以术后焦磷酸测序法获得的结果为金标准。采用t检验或Mann-Whitney U检验分析IDH基因突变组与IDH基因野生组间的2-羟基戊二酸(2HG)、谷氨酸(Glu)、谷氨酰胺(Gln)、2HG/Glu+Gln的差异,对有统计学意义的指标绘制ROC曲线,获得各自预测IDH基因突变状态的效能。结果25例低级别胶质瘤患者中IDH基因突变组19例、IDH基因野生组6例。IDH基因突变组的2HG蓄积浓度、Glu蓄积浓度、Gln蓄积浓度、2HG/Glu+Gln分别为1.42(1.09,1.93)mmol/L、(1.74±1.31)mmol/L、(1.68±0.66)mmol/L、0.55(0.28,0.77),IDH基因野生组分别为0.00(0.00,1.30)mmol/L、(3.28±1.02)mmol/L、(2.55±1.47)mmol/L、0.00(0.00,0.26)。两组间2HG、Glu、2HG/Glu+Gln差异具有统计学意义(P值分别为0.030、0.016、0.004)。2HG/Glu+Gln鉴别IDH突变型与IDH野生型低级别胶质瘤的ROC曲线下面积最大(0.877),对鉴别诊断的灵敏度也最高(84.2%)。结论2HG联合Glu及Gln可有效实现对IDH基因突变状态的无创评估。Objective To investigate the functional imaging parameters that effectively distinguish isocitrate dehydrogenase(IDH)gene mutation status in clinical practice with long echo time(TE)point-resolved spectroscopy(PRESS)MRS.Methods Totally 25 patients with suspected diagnosis of low grade gliomas(LGGs;Grade II)were recruited prospectively and divided into IDH mutation group and IDH wild group according to pathological results in the study.All patients were scanned with long TE PRESS MRS.In addition,IDH mutational status was determined by post-operation Sanger sequencing.The t test or Mann-Whitney U test was used to analyze the differences of 2-hydroxyglutarate(2HG),Glutamate(Glu),Glutamine(Gln)and 2HG/Glu+Gln between the IDH mutation group and the IDH wild group,then ROC curve was plotted with statistically significant indexes to obtain the efficacy of predicting IDH mutation status.Results Of the 25 patients,19 had IDH mutant gliomas and 6 had IDH wild-type gliomas.2HG,Glu,Gln and 2HG/Glu+Gln in IDH mutated group were 1.42(1.09,1.93)mmol/L,(1.74±1.31)mmol/L,(1.68±0.66)mmol/L,0.55(0.28,0.77),respectively;while the corresponding values were 0.00(0.00,1.30)mmol/L,(3.28±1.02)mmol/L,(2.55±1.47)mmol/L,0.00(0.00,0.26)in IDH gene wild type group,respectively.The differences of 2HG,Glu,and 2HG/Glu+Gln between the two groups were statistically significant(P values were 0.030,0.016,0.004,respectively).The area under the ROC curve of 2HG/Glu+Gln was the largest(0.877),and the sensitivity was the highest(84.2%).Conclusion The integration of 2HG with Glu and Gln can effectively realize the noninvasive assessment of IDH mutation status.

关 键 词：神经胶质瘤 异柠檬酸脱氢酶 磁共振波谱成像 

分 类 号：R739.41[医药卫生—肿瘤] R445.2[医药卫生—临床医学]