Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors

Acta Neuropathologica Communications

Vasanta Putluri¹  Venkatrao Vantaku²  Arun Sreekumar²  Nagireddy Putluri²  Ping Zhu³  Guangrong Lu³  Jay-Jiguang Zhu³  Yoshua Esquenazi³  Yuanqing Yan³  Soheil Zorofchian⁴  Leomar Y. Ballester⁴  Roy F. Riascos⁵  Octavio Arevalo⁵ 

[1] Advanced Technology Core, Baylor College of Medicine;Department of Molecular and Cellular Biology, Baylor College of Medicine;Department of Neurosurgery, University of Texas Health Science Center at Houston;Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston;Department of Radiology, University of Texas Health Science Center at Houston;

关键词: CSF;    Metabolites;    Brain tumor;    Glioma;    Hydroxyglutarate;    Liquid biopsy;   

DOI  :  10.1186/s40478-018-0588-z

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown