Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolism.

Abstract:: Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities1-3. Here we identified three metabolic subtypes: glycolytic, oxidative and a mix of glycolytic and oxidative, using mass spectrometry imaging of rapidly excised tumour sections from two patients with GB who were infused with [U-13C]glucose and from spatial transcriptomic analysis of contiguous sections. The phenotypes are not correlated with microenvironmental features, including proliferation rate, immune cell infiltration and vascularization, are retained when patient-derived cells are grown in vitro or as orthotopically implanted xenografts and are robust to changes in oxygen concentration, demonstrating their cell-intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes is large enough to be detected using clinically applicable metabolic imaging techniques. A limitation of the study is that it is based on only two patient tumours, albeit on multiple sections, and therefore represents a proof-of-concept study.

Authors:: A Tsyben, A Dannhorn, G Hamm, M Pitoulias, D-L Couturier, A Sawle, M Briggs, AJ Wright, C Brodie, L Mendil, JL Miller, EC Williams, L Franzén, G De Jong, T Gracia, F Memi, OA Bayraktar, R Adapa, J Rao, A González-Fernández, CRUK Rosetta Grand Challenge Consortium, J Bunch, Z Takats, ST Barry, RJA Goodwin, R Mair, KM Brindle

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