Using arterial-venous analysis to characterize cancer metabolic consumption in patients

Using arterial-venous analysis to characterize cancer metabolic consumption in patients
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使用动静脉分析来表征患者的癌症代谢消耗

DOI:
10.1038/s41467-020-16810-8
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发表时间:
2020-06-23
影响因子:
16.6
通讯作者:
Ge, Woo-ping
Ge, Woo-ping
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xiong, Nanxiang;Gao, Xiaofei;Ge, Woo-ping

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了解肿瘤代谢有望为癌症生物学、诊断和治疗提供新的见解。为了评估人类癌症代谢,在这里,我们报告了一种方法,收集术中血液样本直接上游的动脉和静脉直接下游的脑肿瘤,以及样品从同一患者的足背静脉。在进行靶向代谢组学分析后,我们通过比较动脉供应和静脉引流来表征胶质瘤体内消耗和产生的代谢物。N-乙酰鸟氨酸、D-葡萄糖、腐胺和L-乙酰肉毒碱被神经胶质瘤相对大量地消耗。相反,神经胶质瘤产生相对大量的L-谷氨酰胺、胍丁胺和尿苷5-单磷酸。此外,我们证实,D-2-羟基戊二酸(D-2 HG)是高的异柠檬酸脱氢酶1(IDH 1)突变患者的静脉血浆。通过这些配对比较,我们可以排除通常从肘静脉采集的血浆样本中存在的患者间差异。细胞代谢在许多癌症类型中发生改变,代谢组学的出现使我们能够更多地了解这是如何失调的。在这里,作者报告了一种名为CARVE的方法,用于分析手术期间胶质瘤患者的动脉供应和静脉引流,并确定可能被癌症消耗和产生的代谢物。
Understanding tumor metabolism holds the promise of new insights into cancer biology, diagnosis and treatment. To assess human cancer metabolism, here we report a method to collect intra-operative samples of blood from an artery directly upstream and a vein directly downstream of a brain tumor, as well as samples from dorsal pedal veins of the same patients. After performing targeted metabolomic analysis, we characterize the metabolites consumed and produced by gliomas in vivo by comparing the arterial supply and venous drainage. N-acetylornithine, D-glucose, putrescine, and L-acetylcarnitine are consumed in relatively large amounts by gliomas. Conversely, L-glutamine, agmatine, and uridine 5-monophosphate are produced in relatively large amounts by gliomas. Further we verify that D-2-hydroxyglutarate (D-2HG) is high in venous plasma from patients with isocitrate dehydrogenases1 (IDH1) mutations. Through these paired comparisons, we can exclude the interpatient variation that is present in plasma samples usually taken from the cubital vein. Cellular metabolism is altered in many cancer types and the advent of metabolomics has allowed us to understand more about how this is dysregulated. Here, the authors report a method named CARVE to analyse the arterial supply and venous drainage of glioma patients during surgery and identify the metabolites that may be consumed and produced by the cancer.