Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Neuro-oncology, Changchun, Jilin, China.
BMC Cancer. 2021 Jan 20;21(1):83. doi: 10.1186/s12885-021-07797-6.
Non-invasive diagnosis of IDH1 mutation for gliomas has great clinical significance, and PET has natural advantage to detect metabolism, as IDH mutated gliomas share lower glucose consumption.
Clinical data of patients with gliomas and F-FDG PET were retrospectively reviewed. Receiver operating characteristic curve (ROC) analysis was conducted, and standard uptake value (SUV) was estimated in combination with grades or IDH1 mutation. The glucose consumption was investigated with U251 cells expressing wild-type or mutated IDH1 by glucose assay. Quantification of glucose was determined by HPLC in clinical tissues. Meanwhile, bioinformatics and western blot were applied to analyze the expression level of metabolic enzymes (e.g. HK1, PKM2, PC) in gliomas.
Seventy-one glioma cases were enrolled, including 30 carrying IDH1 mutation. The sensitivity and specificity dependent on SUV (3.85) predicting IDH1 mutation reached 73.2 and 86.7%, respectively. The sensitivity and specificity of differentiating grades by SUVmax (3.1) were 92.3 and 64.4%, respectively. Glucose consumption of U251 IDH1 mutant cells (0.209 ± 0.0472 mg/ml) was obviously lower than IDH1wild-type cells (0.978 ± 0.0773 mg/ml, P = 0.0001) and astrocyte controls (0.335 ± 0.0592 mg/ml, P = 0.0451). Meanwhile, the glucose quantity in IDH1mutant glioma samples were significantly lower than those in IDH1 wild-type tissues (1.033 ± 1.19608 vs 6.361 ± 4.3909 mg/g, P = 0.0051). Silico analysis and western blot confirmed that HK1 and PKM2 in IDH1 wild-type gliomas were significantly higher than in IDH1 mutant group, while PC was significantly higher in IDH1 mutant gliomas.
SUV on PET can predict IDH1 mutation with adequate sensitivity and specificity, as is supported by reduced glucose consumption in IDH1 mutant gliomas.
对于胶质瘤患者，IDH1 突变的无创诊断具有重要的临床意义，而 PET 具有天然的优势来检测代谢，因为 IDH 突变型胶质瘤的葡萄糖消耗较低。
回顾性分析了胶质瘤患者的临床资料和 F-FDG PET 数据。通过绘制受试者工作特征曲线（ROC），并结合分级或 IDH1 突变情况来评估标准摄取值（SUV）。通过葡萄糖测定法检测表达野生型或突变型 IDH1 的 U251 细胞的葡萄糖消耗。通过 HPLC 定量测定临床组织中的葡萄糖。同时，应用生物信息学和 Western blot 分析胶质瘤中代谢酶（如 HK1、PKM2、PC）的表达水平。
共纳入 71 例胶质瘤病例，其中 30 例携带 IDH1 突变。SUV（3.85）预测 IDH1 突变的灵敏度和特异性分别为 73.2%和 86.7%。SUVmax（3.1）预测分级的灵敏度和特异性分别为 92.3%和 64.4%。U251 IDH1 突变细胞的葡萄糖消耗（0.209±0.0472mg/ml）明显低于 IDH1 野生型细胞（0.978±0.0773mg/ml，P=0.0001）和星形胶质细胞对照（0.335±0.0592mg/ml，P=0.0451）。同时，IDH1 突变型胶质瘤样本中的葡萄糖含量明显低于 IDH1 野生型组织（1.033±1.19608 与 6.361±4.3909mg/g，P=0.0051）。生物信息学分析和 Western blot 证实，IDH1 野生型胶质瘤中的 HK1 和 PKM2 明显高于 IDH1 突变型组，而 IDH1 突变型胶质瘤中的 PC 明显升高。
PET 上的 SUV 可以预测 IDH1 突变，具有足够的灵敏度和特异性，这与 IDH1 突变型胶质瘤中葡萄糖消耗减少是一致的。
