2018 Fiscal Year Final Research Report
Comprehensive metabolic analysis in IDH1R132H glioma ; new metabolic biomarkers
| Project/Area Number |
17K16659
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurosurgery
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | 網羅的代謝解析 / β酸化 / 脂質代謝 / イソクエン酸脱水素酵素 / 神経膠腫 / バイオマーカー / MRS / LC model |
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| Outline of Final Research Achievements |
The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples of glioma patients with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells expressing IDH1 or IDH1R132H. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.
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| Free Research Field |
脳腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
脳腫瘍におけるIDH変異は予後良好であるが、他の癌腫においてIDH変異は予後良好マーカーではない。IDH変異の予後良好の機序は不明である。そのため我々は網羅的代謝解析を行いIDH変異の機序を解明した。
今回の研究結果から、IDH正常群の脳腫瘍や他の癌腫における予後良好機序を応用した新規治療などの可能性がある。また、網羅的代謝解析を行って判明した新規バイオマーカー候補物質の可能性がある。つまり、脳腫瘍においてはMRSを用いた術前診断が精度高く可能となり、将来的に手術などを含めた治療戦略の一助となる可能性もある。他の癌腫においては、血液などからバイオマーカー診断を行える可能性もある。
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