Abstract
Abstract Altered metabolism is amongst the hallmarks of cancer including diffuse glioma. We have recently presented a large database with tissue metabolites that are modulated by IDH1 mutation in diffuse glioma. Furthermore, we suggested potential candidate biomarkers for prospective validation that could serve for further refinement of prognostic groups in IDH1-mutated glioma. Glucocorticoids, particularly dexamethasone, are widely used in neuro-oncology and trigger a variety of metabolic effects, e.g. systemic adverse events including steroid-induced diabetes and truncal weight gain. In this subsequent study, we investigated dexamethasone-associated modifications of metabolite profiles in human glioma tissue (n=24 treated with dexamethasone, n=77 without) and in glioma cell lines. We performed ex-vivo Nuclear Magnetic Resonance (NMR) spectroscopy and RNA sequencing to discover comparison-specific metabolites and pathways. Dexamethasone-associated pathways involved increased energy and growth metabolism. Furthermore, we characterized dexamethasone-induced metabolite modulations in glioma cell lines to investigate dexamethasone effects in a rather homogeneous glioma cell population. We investigated the cellular effects of selected significant metabolites in acute cytotoxicity and clonogenic survival assays. Our data provide further insight into dexamethasone-associated metabolic effects in cell lines and tissue that might be relevant for further studies and its use in clinical practice.
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