Affiliation:
1. Department of Chemistry, Umeå University , Umeå , Sweden
2. Department of Radiation Sciences, Oncology, Umeå University , Umeå , Sweden
3. Department of Clinical Science, Neuroscience, Umeå University , Umeå , Sweden
4. Department of Medical Biosciences, Umeå University , Umeå , Sweden
Abstract
Abstract
Background
Gliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.
Methods
Cross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors—oligodendroglioma (n = 31), astrocytoma (n = 31) and glioblastoma (n = 162)—were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2–4, and MGMT promoter methylation.
Results
Distinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides, and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.
Conclusion
Key metabolic differences exist across adult glioma subtypes.
Funder
Umeå University Hospital
Swedish Research Council
Swedish Cancer Society
Cancer Research Foundation in Northern Sweden
Lions Cancer Research Fund
Sjöberg Foundation
Research Fund for Clinical Neuroscience at Umeå University Hospital
Jämtland County Cancer and Nursing Fund
County Council of Jämtland-Härjedalen
Publisher
Oxford University Press (OUP)
Subject
Cancer Research,Neurology (clinical),Oncology
Cited by
38 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献