An integrated genomic and metabolomic approach for defining survival time in adult oligodendrogliomas patients
An integrated genomic and metabolomic approach for defining survival time in adult oligodendrogliomas patients
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DOI：
10.1007/s11306-019-1522-5
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发表时间：
2019-05-01
期刊：
影响因子：
3.6
通讯作者：
Namer, Izzie Jacques
中科院分区：
文献类型：
--
作者：
Bund, Caroline;Guergova-Kuras, Mariana;Namer, Izzie Jacques
常见获得性突变的鉴定表明，无论组织学分类如何，少突胶质细胞瘤患者具有不同的生物学和不同的预后。更好地了解分子特征及其代谢途径是必不可少的。目的探讨肿瘤代谢组学、6种基因组畸变（异柠檬酸脱氢酶1 [IDH1]突变、1p/19q编码缺失、肿瘤蛋白p53 [TP53]突变、o -6-甲基鸟嘌呤- dna甲基转移酶[MGMT]启动子甲基化、表皮生长因子受体[EGFR]扩增、磷酸和紧张素同源物[PTEN]甲基化）与患者生存时间的关系。方法应用H-1高分辨率魔角旋转（HRMAS）核磁共振（NMR）技术对72例切除的少突胶质细胞瘤进行分析。结果IDH1、TP53、1p19q编码缺失、MGMT启动子甲基化降低了患者的相对死亡风险，而PTEN甲基化和EGFR扩增与预后不良相关。2-羟戊二酸（2HG）、n -乙酰-天冬氨酸（NAA）、肌醇浓度和甘油胆碱/磷脂胆碱（GPC/PC）比值升高是预后良好的因素。增加丝氨酸、甘氨酸、谷氨酸和丙氨酸的浓度导致死亡的相对风险增加。结论hrmas核磁共振谱提供了少突胶质细胞瘤代谢组学的准确信息，为寻找新的生存指标提供了可能。它可以快速表征完整组织，并可作为术中方法使用。
IntroductionThe identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential.ObjectivesThe aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O-6-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time.MethodsWe applied H-1 high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas.ResultsThe presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death.ConclusionHRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.