Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors.
Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors.
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DOI：
10.1186/s40478-018-0588-z
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发表时间：
2018-08-31
影响因子：
7.1
通讯作者：
Zhu JJ
中科院分区：
文献类型：
--
作者：
Ballester LY;Lu G;Zorofchian S;Vantaku V;Putluri V;Yan Y;Arevalo O;Zhu P;Riascos RF;Sreekumar A;Esquenazi Y;Putluri N;Zhu JJ
癌细胞改变了细胞的新陈代谢。与关键代谢途径(如异柠檬酸脱氢酶1和2，IDH1/IDH2)相关的基因突变是包括中枢神经系统(CNS)肿瘤在内的癌症的重要驱动因素。因此，我们推测中枢神经系统肿瘤细胞的异常代谢状态导致了脑脊液中代谢产物水平的异常，不同的中枢神经系统肿瘤类型与脑脊液代谢产物水平的特定变化有关。为了验证这一假设，我们使用质谱仪分析了来自没有癌症病史的患者(n = 8)和各种中枢神经系统肿瘤类型(n = 23)(即胶质瘤IDH突变、胶质瘤IDH野生型、转移性肺癌和转移性乳腺癌)的脑脊液样本中的129种不同的代谢物。无监督的分级聚类分析显示了肿瘤特定的代谢特征，有助于区分肿瘤类型和脑脊液分析。我们发现对照组患者的脑脊液和原发或转移的中枢神经系统肿瘤患者的脑脊液中43种代谢物的丰度存在差异。通路分析揭示了IDH突变型和IDH野生型胶质瘤之间不同代谢途径(如甘氨酸、胆碱和蛋氨酸的降解、双乙胺的生物合成和糖酵解途径等)的变化。此外，IDH突变的胶质瘤患者的脑脊液中D-2-羟基戊二酸的水平高于其他肿瘤类型的患者或对照组。本研究表明，脑脊液代谢产物的分析可作为诊断和监测原发或转移性中枢神经系统肿瘤患者的临床有用工具。本文的在线版本(10.1186/s40478-0180588-z)包含补充材料，可供授权用户使用。
Cancer cells have altered cellular metabolism. Mutations in genes associated with key metabolic pathways (e.g., isocitrate dehydrogenase 1 and 2, IDH1/IDH2) are important drivers of cancer, including central nervous system (CNS) tumors. Therefore, we hypothesized that the abnormal metabolic state of CNS cancer cells leads to abnormal levels of metabolites in the CSF, and different CNS cancer types are associated with specific changes in the levels of CSF metabolites. To test this hypothesis, we used mass spectrometry to analyze 129 distinct metabolites in CSF samples from patients without a history of cancer (n = 8) and with a variety of CNS tumor types (n = 23) (i.e., glioma IDH-mutant, glioma-IDH wildtype, metastatic lung cancer and metastatic breast cancer). Unsupervised hierarchical clustering analysis shows tumor-specific metabolic signatures that facilitate differentiation of tumor type from CSF analysis. We identified differences in the abundance of 43 metabolites between CSF from control patients and the CSF of patients with primary or metastatic CNS tumors. Pathway analysis revealed alterations in various metabolic pathways (e.g., glycine, choline and methionine degradation, dipthamide biosynthesis and glycolysis pathways, among others) between IDH-mutant and IDH-wildtype gliomas. Moreover, patients with IDH-mutant gliomas demonstrated higher levels of D-2-hydroxyglutarate in the CSF, in comparison to patients with other tumor types, or controls. This study demonstrates that analysis of CSF metabolites can be a clinically useful tool for diagnosing and monitoring patients with primary or metastatic CNS tumors. The online version of this article (10.1186/s40478-018-0588-z) contains supplementary material, which is available to authorized users.
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DOI：
10.1158/1078-0432.ccr-15-2965
发表时间：
2016-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kalinina J;Ahn J;Devi NS;Wang L;Li Y;Olson JJ;Glantz M;Smith T;Kim EL;Giese A;Jensen RL;Chen CC;Carter BS;Mao H;He M;Van Meir EG
通讯作者：
Van Meir EG
影响因子：
16.6
作者：
De Mattos-Arruda L;Mayor R;Ng CKY;Weigelt B;Martínez-Ricarte F;Torrejon D;Oliveira M;Arias A;Raventos C;Tang J;Guerini-Rocco E;Martínez-Sáez E;Lois S;Marín O;de la Cruz X;Piscuoglio S;Towers R;Vivancos A;Peg V;Ramon y Cajal S;Carles J;Rodon J;González-Cao M;Tabernero J;Felip E;Sahuquillo J;Berger MF;Cortes J;Reis-Filho JS;Seoane J
通讯作者：
Seoane J
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
--
作者：
Yoo BC;Lee JH;Kim KH;Lin W;Kim JH;Park JB;Park HJ;Shin SH;Yoo H;Kwon JW;Gwak HS
通讯作者：
Gwak HS
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y