IDH1基因突变对胶质瘤诊断及预后意义

目的通过对幕上胶质瘤细胞IDH1基因突变检测,研究IDH1基因突变对胶质瘤临床诊断及预后的意义。方法提取315例幕上胶质瘤(WHOⅠ级3例、Ⅱ级95例、Ⅲ级37例、Ⅳ级180例)患者手术切除标本IDH1基因DNA,经聚合酶链反应扩增后直接测序,同时对患者年龄、性别、肿瘤生长部位、切除范围、Karnofsky生活质量评分和生存时间等进行多因素分析,了解IDH1基因突变对患者预后的影响。结果经对315例胶质瘤标本测序共发现112例发生IDH1基因突变,突变率约为35.56%,均为R132H型突变。不同病理分级胶质瘤基因突变率分别为WHOⅡ级72.63%(69/95)、Ⅲ级24.32%(9/37)、Ⅳ级18.89%(34/180),不同级别突变率比较差异具有统计学意义(均P=0.000);WHOⅣ级胶质瘤发生突变的患者中18例为原发性、16例为继发性胶质母细胞瘤,突变率分别为11.39%(18/158)和72.73%(16/22),后者显著高于前者且差异有统计学意义(χ2=23.654,P=0.001)。生存分析显示,IDH1基因突变对患者预后有显著影响。结论 WHOⅡ～Ⅳ级胶质瘤均可发生IDH1基因突变,其中以WHOⅡ级和Ⅳ级中的继发性胶质母细胞瘤基因突变率较高。IDH1基因突变对患者生存时间有明显影响,发生IDH1突变者预后良好,提示IDH1基因突变对胶质瘤患者诊断及预后有重要临床预测价值。     

基于改进LeNet-5模型的WHO Ⅱ/Ⅲ级脑胶质瘤影像自动分级的临床研究

目的 探讨基于改进LeNet-5模型的WHO 11/Ⅲ级脑胶质瘤影像自动分级的临床应用价值.方法 收集经手术病理证实的98例WHO Ⅱ级和Ⅲ级胶质瘤患者的MRI资料;按照就诊时间顺序将前67例患者作为训练集,后31例患者作为测试集.首先,用深度学习技术及训练集的760张MRI T2WI图像,在卷积神经网络下(LeNet...     

不同病理类型和级别胶质瘤细胞IDH1基因突变情况分析

目的探讨国人不同病理类型和级别胶质瘤细胞中异柠檬酸脱氢酶1（IDH1）基因突变情况及其临床意义。方法应用mIDH1 R132H免疫组化学法检测87例国人不同病理类型和级别的胶质瘤标本中IDH1基因突变发生率,分析不同病理类型、不同WHO级别和不同年龄的IDH1基因突变情况。结果 87例国人胶质瘤标本中有45例（51.7%）检出IDH1基因突变,并与胶质瘤的病理类型、WHO分级以及年龄等具有相关性。结论 IDH1基因突变在WHOⅡ、Ⅲ级胶质瘤中的发生率较高,并在胶质瘤的发生、发展过程中起重要作用。     

常规MRI纹理分析鉴别WHO Ⅱ级与Ⅲ级胶质瘤的 价值

目的 探讨常规MRI纹理分析在WHO Ⅱ级与Ⅲ级胶质瘤鉴别中的临床价值。方法 回顾性分析经病理证实的40例WHO Ⅱ级和46例WHO Ⅲ级胶 质瘤的常规MRI影像。在MaZda上勾画肿瘤最大层面进行纹理分析,选出与肿瘤级别显著相关的特征纹理参数并统计分析各特征纹理参数的诊断效能。 结果 四种MRI序列（包括T1WI、T2WI、FLAIR、T1WI增强）鉴别WHO Ⅱ级和Ⅲ级胶质瘤的最小误判率为9.30%,出现在T2WI序列中。多元Logistic回归 分析显示,T2WI序列中熵（OR=2.497;P=0.009 ）及游程长非均匀度因子（OR=1.844;P=0.011）与胶质瘤级别独立相关。根据ROC曲线分析结果,以 熵=2.46为阈值鉴别WHO Ⅱ级和Ⅲ级胶质瘤的曲线下面积为0.843,敏感性、特异性分别为0.814、0.767;以游程长非均匀度因子=363.22为阈值鉴别 WHO Ⅱ级和Ⅲ级胶质瘤的曲线下面积为0.808,敏感性、特异性分别为0.794、0.778。结论 常规MRI纹理分析有助于鉴别WHO Ⅱ级与Ⅲ级胶质瘤, T2WI纹理参数中熵及游程长非均匀度因子的鉴别诊断价值最高。     

MRI影像组学在脑胶质瘤分级中的价值研究

目的采用MRI影像组学方法对胶质瘤的高、低级别进行术前评估。方法纳入154例经病理证实的脑胶质瘤病人,其中WHO Ⅱ级(低级别胶质瘤)75例,WHO Ⅲ~Ⅳ级(高级别胶质瘤)79例,随机分为训练集和验证集各77例。应用受试者工作特征(ROC)曲线下面积(AUC)表示训练集和验证集性能。利用影像组学标签联合病理学检测构建评估高、低级别脑胶质瘤的预测模型,并采用影像组学诺模图反应测试模型。结果采用LASSO方法在388个影像组学特征中选择3个标签特征,联合病理结果进行二分类建模。诺模图显示联合影像组学标签及病理结果构建的模型图可以显著提高诊断效能。训练集中AUC达到0.850,特异性达81.8%,敏感性为77.3%;验证集中AUC达0.836,特异性达83.3%,敏感性为77.3%。LASSO构建的模型评估决策曲线高于其他模型。结论 MRI影像组学方法可在术前帮助区分脑胶质瘤的高、低级别。     

173例胶质瘤预后的影响因素分析

目的 探讨影响胶质瘤预后的相关因素。方法 对2000年1月至2009年12月在中山大学肿瘤防治中心首次手术病理确诊为胶质瘤的临床资料进行回顾性分析,并排除因非肿瘤因素死亡患者,采用Kaplan-Meier法进行生存率估计及Cox比例风险回归模型进行预后多因素分析。结果 本组纳入胶质瘤173例,其中WHO Ⅰ级10例,Ⅱ级61例,Ⅲ级53例,Ⅳ级49例;98例术后接受放疗[高级别胶质瘤（WHOⅢ~Ⅳ级）61例,低级别胶质瘤（WHO Ⅰ~Ⅱ级）37例];60例术后接受化疗（高级别胶质瘤46例,低级别胶质瘤14例）。本组患者1、3、5年总体生存率分别为74.0%、42.2%、32.4%;WHO Ⅰ、Ⅱ、Ⅲ、Ⅳ级的 5年生存率分别为80.0%、52.5%、24.5%、6.1%。分层分析显示术后辅助放化疗显著影响高级别胶质瘤生存率（P <0.05）。Cox比例风险回归模型分析结果 显示,年龄>40岁（RR=1.603;P=0.019）、WHO Ⅲ~Ⅳ分级（RR=2.311;P <0.001）、肿瘤未全切（RR=2.108;P <0.001）、术后未放疗（RR=1.652;P=0.008）是影响胶质瘤总体生存率的独立危险因素。结论 本组病例的分析结果 提示,发病年龄≤40岁、WHO级别低、肿瘤全切的胶质瘤患者预后好;术后进行放疗可以提高胶质瘤的疗效。     

术前血液炎性标记物与胶质瘤病理分级IDH1基因表型的相关性研究

目的探讨胶质瘤患者术前外周血液炎症指标与胶质瘤病理分级、IDH1基因表型的相关性。方法回顾性分析2015-12—2020-09在徐州医科大学附属医院首次接受手术治疗的465例胶质瘤患者的临床病理资料,通过Kruskal-Wallis进行非参数检验、Spearman相关性分析、受试者工作特性曲线(ROC曲线)分析术前外周血中性粒细胞-淋巴细胞比值(NLR)、衍生中性粒细胞-淋巴细胞比值(dNLR)、血小板-淋巴细胞比值(PLR)、单核细胞-淋巴细胞比值(MLR)、预后营养指数(PNI)与胶质瘤病理分级、IDH1基因表型的关系。结果共纳入465例胶质瘤患者(其中WHOⅠ级30例,WHOⅡ级134例,WHOⅢ级88例,WHOⅣ级213例)与450例健康对照者。非参数检验显示不同病理分级的胶质瘤患者术前NLR、dNLR、PLR和MLR的表达存在显著差异(P<0.05)。Spearman相关性分析显示胶质瘤患者术前NLR、PLR、MLR与WHO分级均存在正相关性(r分别为0.379、0.238、0.226,P<0.01),而胶质瘤患者术前PNI与病理分级有明显的负相关性(r=0.411,P<0.01)。IDH1突变与PNI呈正相关(r=0.108,P<0.05),IDH1突变与病理分级、NLR均呈负相关(r分别为0.353、0.105,P<0.05)。与健康对照组相比,胶质母细胞瘤患者NLR的受试者工作特性曲线下面积(AUC)为0.816(95%CI 0.764~0.848),dNLR为0.588(95%CI 0.537~0.640),PLR为0.673(95%CI 0.624~0.773),MLR为0.682(95%CI 0.633~0.731)。术前外周血液炎症指标对胶质母细胞瘤的预测价值显著高于Ⅰ~Ⅲ级胶质瘤患者。结论胶质瘤患者术前NLR、dNLR、PLR、MLR、PNI与胶质瘤病理分级、IDH1基因表型相关,对术前预测胶质瘤的病理分级有一定的参考价值。     

3.0T MRI弥散张量成像对脑胶质瘤分级的诊断价值探讨

目的评价3.0T MRI弥散张量成像(DTI)对脑胶质瘤分级的诊断价值。方法回顾性分析85例组织病理学证实为脑胶质瘤患者的影像学资料,比较肿瘤WHO分级与肿瘤实体感兴趣区域的表观弥散系数(ADC)值和各项异性参数(FA)值。结果 WHO分级Ⅱ级、Ⅲ级、Ⅳ级分别为47例、22例、16例;WHO分级Ⅱ级ADC值高于Ⅲ级或Ⅳ级(P均0.05),Ⅲ级ADC值高于Ⅳ级(P0.05);WHO分级Ⅱ级FA值低于Ⅳ级(P0.05),但Ⅱ级与Ⅲ级之间的FA值差异无统计学意义(P0.05)。结论 3.0T MRI弥散张量成像(DTI)在脑胶质瘤分级上具有重要意义,能够为术前治疗方案优化和预后判断提供支持。     

11C-Met PET与MRI影像融合技术在胶质瘤术前评价和术中导航中的应用价值

研究背景随着多模态影像融合技术在临床的应用,11C-Met PET与MRI融合技术也应用于临床,本研究通过比较胶质瘤在11C-Met PET与MRI中不同影像显示结果,探讨11C-Met PET与MRI影像融合技术在脑胶质瘤外科手术前评价、术中导航和手术切除过程中的应用价值。方法手术前于神经导航工作站对25例胶质瘤患者进行11C-Met PET与MRI影像融合,勾画肿瘤边界、计算肿瘤体积并进行分类。结果据影像学分类,25例胶质瘤患者中1例Ⅱ级、6例Ⅲ级和8例Ⅳ级MRI所显示的肿瘤灶轮廓大部分位于PET内(Ⅰ类);2例Ⅲ级PET所显示的肿瘤灶轮廓大部分位于MRI内(Ⅱ类);6例Ⅱ级和2例Ⅲ级MRI与PET显示的病灶轮廓无从属关系(Ⅲ类)。结论 PET在揭示胶质瘤增殖活性和描述肿瘤界限方面具有特殊优势,通过MRI与PET所显示的肿瘤轮廓关系,可用于术前初步预测肿瘤病理分级,有助于制定详细的手术计划。     

^11C—MetPET与MRI影像融合技术在胶质瘤术前评价和术中导航中的应用价值

研究背景随着多模态影像融合技术在临床的应用,^11C—MetPET与MRI融合技术也应用于临床,本研究通过比较胶质瘤在^11C-MetPET与MRI中不同影像显示结果,探讨^11C—MetPET与MRI影像融合技术在脑胶质瘤外科手术前评价、术中导航和手术切除过程中的应用价值。方法手术前于神经导航工作站对25例胶质瘤患者进行^11C—MetPET与MRI影像融合,勾画肿瘤边界、计算肿瘤体积并进行分类。结果据影像学分类,25例胶质瘤患者中1例Ⅱ级、6例Ⅲ级和8例Ⅳ级MRI所显示的肿瘤灶轮廓大部分位于PET内（I类）;2例Ⅲ级PET所显示的肿瘤灶轮廓大部分位于MRI内（Ⅱ类）;6例Ⅱ级和2例Ⅲ级MRI与PET显示的病灶轮廓无从属关系（Ⅲ类）。结论PET在揭示胶质瘤增殖活性和描述肿瘤界限方面具有特殊优势,通过MRI与PET所显示的肿瘤轮廓关系,可用于术前初步预测肿瘤病理分级,有助于制定详细的手术计划。     

MRI影像组学模型预测脑胶质瘤IDH-1基因突变和Ki-67表达水平的价值

目的 探讨MRI影像组学模型预测脑胶质瘤IDH-1基因突变和Ki-67表达水平的价值。方法 回顾性分析2017年1月至2021年6月经术后病理证实的77例胶质瘤的临床资料,其中72例IDH-1基因检测结果完整（IDH-1组）,75例Ki-67检测结果完整（Ki-67组）。基于MRI T2WI序列选择感兴趣区域,运用Python提取影像组学特征,先用两独立样本t检验进行筛选,再用LASSO回归进一步筛选特征值。使用随机森林和参数优化后的支持向量机两种分类器建立影像组学模型,绘制受试者工作特征曲线,并计算曲线下面积判断模型预测IDH-1基因突变和Ki-67表达水平的灵敏度、特异度。结果 IDH-1组t检验筛选出47个特征,再通过LASSO回归筛选出11个特征。Ki-67组t检验筛选出17个特征,再通过LASSO回归筛选出10个特征。支持向量机和随机森林两种方法建立的影像组学模型预测胶质瘤IDH-1基因突变和Ki-67表达水平均有较高的预测效能,预测准确率均超过88.0%。结论 MRI影像组学模型对预测胶质瘤IDH-1基因突变和Ki-67表达水平具有较高的应用价值,为胶质瘤术前预测提供了新思路。     

脑胶质瘤病人血清β2微球蛋白含量的变化

目的 探讨脑胶质瘤病人血清β2微球蛋白（β2-MG）含量的变化。方法 收集2015~2017年手术切除及病理确诊的胶质瘤标本124例，其中WHO Ⅰ级9例，Ⅱ级28例，Ⅲ级34例，Ⅳ级53例。术前2~3 d采取静脉血，通过胶乳免疫比浊法检测血清β2-MG含量；并使用石蜡包埋的胶质瘤组织分别通过毛细管电泳法检测基因异柠檬酸脱氢酶1（IDH1）突变和PCR荧光探针法检测06-甲基鸟嘌呤DNA甲基转移酶（MGMT）基因甲基化状态。结果 WHO Ⅳ级胶质瘤病人血清β2-MG含量显著高于其他级别（WHO Ⅰ~Ⅲ级）胶质瘤（P<0.05）。IDH1突变型胶质瘤病人血清β2-MG含量显著低于野生型病人（P<0.05）。MGMT甲基化胶质瘤病人血清β2-MG含量与非甲基化病人之间无明显差异（P>0.05）。结论 血清β2-MG含量对于WHO Ⅳ级胶质瘤与其他级别件胶质瘤的鉴别以及IDH1突变与野生型的鉴别中可能具有重要的参考意义。     

An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy

Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma-related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p = 0.043 for the WHO grade II gliomas, p = 0.002 for the grade III gliomas and p = 0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme.     

人脑胶质瘤 IDH1基因突变与临床病理类别的关系

目的探究不同病理类型和级别的胶质瘤患者中异柠檬酸脱氢酶1（IDH1）基因突变情况及其临床意义。 方法选取厦门大学附属第一医院神经外科自2014年1月至2017年9月收治并实施手术的胶质瘤患者76例,通过免疫组化检测并鉴定各病理组织样本中IDH1基因突变情况,分析不同病理类型、不同WHO级别和不同年龄患者IDH1基因突变率。 结果76例胶质瘤标本中,共检出37例IDH1基因突变,总突变率48.68%。各种病理类型突变率由高至低分别为：弥漫性星形细胞瘤（71.43%）、间变型少突星形细胞瘤（71.43%）、少突胶质瘤（66.67%）、少突星形细胞瘤（66.67%）、间变型星形细胞瘤（63.64%）、胶质母细胞瘤（34.62%）。IDH1基因突变型的年龄普遍较野生型更小,其中,弥漫性星形细胞瘤、少突星形细胞瘤、间变型星形细胞瘤、间变型少突星形细胞瘤及胶质母细胞瘤样本中,IDH1基因突变型患者平均年龄均低于野生型患者,差异具有统计学意义（P<0.05）。 结论IDH1基因突变在WHOⅡ、Ⅲ级胶质瘤中的发生率较高,并在胶质瘤的发生、发展过程中起重要作用。     

lncRNA MIR4435-2HG的表达水平及甲基化状态与脑胶质瘤病理分级的关系

目的 探讨长链非编码RNA MIR4435-2HG的表达水平及甲基化状态与脑胶质瘤病理分级的关系.方法 选取2019年1～12月手术切除的脑胶质瘤组织110例和颅脑损伤内减压术中切除正常脑组织20例(对照组).采用实时荧光定量PCR和甲基化特异性PCR检测组织和血清MIR4435-2HG水平及甲基化状态.结果 110例...     

IDH1 R132H突变对不同级别胶质瘤的影响及相关因素分析

目的 检测人脑不同级别胶质瘤组织中IDH1 R132H突变及胶质瘤细胞系IDH1表达情况,探讨IDH1 R132H突变对不同级别胶质瘤的影响.方法 采用q-PCR法检测U87、U251、LN-229、HS683、U118等胶质瘤细胞系中IDH1表达情况,回顾性收集70例经手术切除、病理确诊的胶质瘤组织标本(实验组)及同...     

合并癫痫的幕上低级别胶质瘤病人癫痫预后的影响因素分析

目的探讨合并癫痫的幕上低级别胶质瘤病人癫痫预后的影响因素。方法回顾性分析2015年6月至2019年1月手术治疗的80例合并癫痫的幕上低级别胶质瘤的临床资料。术后1年,采用Engel分级评估癫痫预后,Ⅰ级为预后良好,Ⅱ~Ⅳ级为预后不良。用多因素logistic回归分析检验影响癫痫预后的影响因素;受试者工作特征(ROC)曲线分析术前癫痫发作频率预测癫痫预后的价值。结果80例中,术后癫痫预后良好59例,预后不良21例。多因素logistic回归分析结果显示,异柠檬酸脱氢酶(IDH)1突变和术前癫痫发作频率高是胶质瘤病人术后癫痫的独立危险因素(P<0.05),全切肿瘤和术后化疗是保护性因素(P<0.05)。术前癫痫发作频率预测癫痫预后的ROC曲线下面积为0.805(95%置信区间0.685~0.914;P<0.05);当术前癫痫发作频率≥2次/月时,预测术后癫痫预后不良的灵敏度和特异度分别为92.86%和46.85%。结论IDH1突变和术前癫痫发作频率高是合并癫痫的幕上低级别胶质瘤病人癫痫预后不良的危险因素,而肿瘤全切除和术后化疗明显改善癫痫预后。     

Reliability of noncontrast-enhancing tumor as a biomarker of IDH1 mutation status in glioblastoma

Isocitrate dehydrogenase 1 (IDH1) mutations in gliomas have been associated with a frontal lobe location and a greater proportion of noncontrast-enhancing tumour (nCET). The purpose of our study was to validate the utility of MRI imaging features in predicting IDH1 mutations in glioblastomas. Pre-operative MRIs of new glioblastoma patients, consisting of at least FLAIR and T1-weighted post-contrast sequences, were reviewed by a neuroradiologist based primarily on the VASARI feature set. IDH1 mutation testing was performed on all patients using immunohistochemistry. 153 patients met the inclusion criteria, of whom five had IDH1 mutations (3.3%). A frontal lobe location had equivalent frequency in both the IDH1-mutated and IDH1-wildtype cohorts (p = 1.000). Three (60%) of the IDH1-mutated tumours had >33% nCET, compared to 21% of IDH1-wildtype (p = 0.073). 12 tumours had a frontal lobe epicentre and >33% nCET, all being IDH1-wildtype. All five IDH1-mutated tumours had either a frontal lobe epicentre or >33% nCET, but none had both these features. Our results question the strength of the association between frontal lobe glioblastomas with substantial nCET and IDH1 mutations, as these features are also relatively frequent in IDH1-wildtype tumours, which are much more common. MRI is thus more useful for ruling out an IDH1 mutation rather than strongly suggesting its presence: if a particular glioblastoma does not have a frontal lobe epicentre and has less than 33% nCET, it can be predicted to be IDH1-wildtype with a high degree of confidence.     

IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy

ObjectiveIsocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II–IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency.MethodsThis was a retrospective study. Patients with grades II–IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A — postoperative seizure freedom; Group B — 1–11 seizures over 12 months (less than one seizure per month); and Group C — greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.ResultsOne hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12 months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p = 0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p = 0.032) and Group B (RR 9.70, p = 0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p = 0.004).SignificanceIn patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.