Cell-intrinsic metabolic phenotypes identified in glioblastoma patients using mass spectrometry imaging of 13C-labeled glucose metabolism

Abstract

Transcriptomic studies attempted to classify glioblastoma (GB) into subtypes that predict survival and that have different therapeutic vulnerabilities1-3. Here we identified three metabolic subtypes: glycolytic, oxidative and a mixed glycolytic/oxidative by mass spectrometry imaging of rapidly excised tumour sections from two GB patients 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 vascularisation, 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 are 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.