Diagnostic value of tumor metabolites in metabolome analysis for glioma patients

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293309
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kobe University
• Principal Investigator: Kohmura Eiji 神戸大学, 医学(系)研究科(研究院), 教授 (30225388)
• Co-Investigator(Kenkyū-buntansha): SASAYAMA Takashi 神戸大学, 医学部附属病院, 講師 (10379399) ; TANAKA Kazuhiro 神戸大学, 医学(系)研究科(研究院), 研究員 (70467661) ; HOSODA Koukichi 神戸大学, 医学(系)研究科(研究院), 准教授 (90403261) ; MIZUKAWA Katsu 神戸大学, 医学部附属病院, 助教 (80403260) ; SASAKI Ryohei 神戸大学, 医学部附属病院, 教授 (30346267)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: glioma / metabolome / IDH / glutamate

Outline of Final Research Achievements

In this study, we aimed to determine the additional value of other metabolites in predicting IDH1 mutations with conventional MRS.
RESULTS: A metabolomic analysis demonstrated higher levels of 2HG in IDH1 mutant glioma cells and surgical tissues. Interestingly, glutamate levels were significantly decreased in IDH1 mutant gliomas. Through an analysis of metabolic enzyme genes in glutamine pathways, it was shown that the expressions of branched-chain amino acid transaminase 1 were reduced and glutamate dehydrogenase levels were elevated in IDH1 mutant gliomas. Conventional MRS detection of glutamate and 2HG resulted in a high diagnostic accuracy (sensitivity 72%, specificity 96%) for IDH1 mutant glioma.
CONCLUSIONS: IDH1 mutations alter glutamate metabolism. Combining glutamate levels optimizes the 2HG-based monitoring of IDH1 mutations via MRS and represents a reliable clinical application for diagnosing IDH1 mutant gliomas.

Free Research Field

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