Abstract
Metabolomics has recently undergone rapid development; however, metabolomic analysis in cerebrospinal fluid (CSF) is not a common practice. We analyzed the metabolite profiles of preoperative CSF samples from 32 patients with histologically confirmed glioma using gas chromatography/mass spectrometry (GC/MS). We assessed how alterations in the metabolite levels were related to the World Health Organization (WHO) tumor grades, tumor location, gadolinium enhancement on magnetic resonance imaging (MRI), and the isocitrate dehydrogenase (IDH) mutation status. Sixty-one metabolites were identified in the CSF from glioma patients using targeted, quantitative and non-targeted, semi-quantitative analysis. The citric and isocitric acid levels were significantly higher in the glioblastoma (GBM) samples than in the grades I–II and grade III glioma samples. In addition, the lactic and 2-aminopimelic acid levels were relatively higher in the GBM samples than in the grades I–II glioma samples. The CSF levels of the citric, isocitric, and lactic acids were significantly higher in grade I–III gliomas with mutant IDH than in those with wild-type IDH. The tumor location and enhancement obtained using MRI did not significantly affect the metabolite profiles. Higher CSF levels of lactic acid were statistically associated with a poorer prognosis in grades III–IV malignant gliomas. Our study suggests that the metabolomic analysis of CSF from glioma patients may be useful for predicting the glioma grade, metabolic state, and prognosis of gliomas.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-013-1090-x) contains supplementary material, which is available to authorized users.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.M
In malignant gliomas alone, higher cerebrospinal fluid (CSF) levels of lactic acid were significantly associated with having a shorter overall survival (OS) (Fig. 2c)
The 13C-nuclear MR spectroscopy measurements have demonstrated that glioblastoma cells convert as much as 90 % of the glucose that they acquire into lactic acid in vitro [32]
Summary
Electronic supplementary material The online version of this article (doi:10.1007/s11060-013-1090-x) contains supplementary material, which is available to authorized users. M. Yoshida Division of Metabolomics Research, Kobe University Graduate School of Medicine, Kobe, Japan. Previous reports have indicated that these mutations are frequently observed in astrocytic and oligodendroglial tumors of grades II and III [14,15,16,17]. Because these enzymes catalyze reactions of energy metabolism, IDH mutations may alter global cellular metabolism [18]. We conducted a GC/MS-based metabolomic analysis of CSF samples from 32 glioma patients. Our study indicates that a metabolomic analysis of CSF from glioma patients may be useful for predicting the malignancy grade and IDH mutation status
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