Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR

Abstract Gliomas are one of the most common types of brain tumors. Given low survival and high treatment resistance rates, particularly for high grade gliomas, there is a need for specific biomarkers that can be used to stratify patients for therapy and monitor treatment response. Recent work has de...

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Autores principales:	Selin Ekici, Benjamin B. Risk, Stewart G. Neill, Hui-Kuo Shu, Candace C. Fleischer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fdcc5c2f91e24a72a68db8e571d3162b
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spelling	oai:doaj.org-article:fdcc5c2f91e24a72a68db8e571d3162b2021-12-02T16:08:47ZCharacterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR10.1038/s41598-020-76982-72045-2322https://doaj.org/article/fdcc5c2f91e24a72a68db8e571d3162b2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-76982-7https://doaj.org/toc/2045-2322Abstract Gliomas are one of the most common types of brain tumors. Given low survival and high treatment resistance rates, particularly for high grade gliomas, there is a need for specific biomarkers that can be used to stratify patients for therapy and monitor treatment response. Recent work has demonstrated that metabolic reprogramming, often mediated by inflammation, can lead to an upregulation of glutamine as an energy source for cancer cells. As a result, glutamine pathways are an emerging pharmacologic target. The goal of this pilot study was to characterize changes in glutamine metabolism and inflammation in human glioma samples and explore the use of glutamine as a potential biomarker. 1H high-resolution magic angle spinning nuclear magnetic resonance spectra were acquired from ex vivo glioma tissue (n = 16, grades II–IV) to quantify metabolite concentrations. Tumor inflammatory markers were quantified using electrochemiluminescence assays. Glutamate, glutathione, lactate, and alanine, as well as interleukin (IL)-1β and IL-8, increased significantly in samples from grade IV gliomas compared to grades II and III (p ≤ .05). Following dimension reduction of the inflammatory markers using probabilistic principal component analysis, we observed that glutamine, alanine, glutathione, and lactate were positively associated with the first inflammatory marker principal component. Our findings support the hypothesis that glutamine may be a key marker for glioma progression and indicate that inflammation is associated with changes in glutamine metabolism. These results motivate further in vivo investigation of glutamine as a biomarker for tumor progression and treatment response.Selin EkiciBenjamin B. RiskStewart G. NeillHui-Kuo ShuCandace C. FleischerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Selin Ekici Benjamin B. Risk Stewart G. Neill Hui-Kuo Shu Candace C. Fleischer Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR
description	Abstract Gliomas are one of the most common types of brain tumors. Given low survival and high treatment resistance rates, particularly for high grade gliomas, there is a need for specific biomarkers that can be used to stratify patients for therapy and monitor treatment response. Recent work has demonstrated that metabolic reprogramming, often mediated by inflammation, can lead to an upregulation of glutamine as an energy source for cancer cells. As a result, glutamine pathways are an emerging pharmacologic target. The goal of this pilot study was to characterize changes in glutamine metabolism and inflammation in human glioma samples and explore the use of glutamine as a potential biomarker. 1H high-resolution magic angle spinning nuclear magnetic resonance spectra were acquired from ex vivo glioma tissue (n = 16, grades II–IV) to quantify metabolite concentrations. Tumor inflammatory markers were quantified using electrochemiluminescence assays. Glutamate, glutathione, lactate, and alanine, as well as interleukin (IL)-1β and IL-8, increased significantly in samples from grade IV gliomas compared to grades II and III (p ≤ .05). Following dimension reduction of the inflammatory markers using probabilistic principal component analysis, we observed that glutamine, alanine, glutathione, and lactate were positively associated with the first inflammatory marker principal component. Our findings support the hypothesis that glutamine may be a key marker for glioma progression and indicate that inflammation is associated with changes in glutamine metabolism. These results motivate further in vivo investigation of glutamine as a biomarker for tumor progression and treatment response.
format	article
author	Selin Ekici Benjamin B. Risk Stewart G. Neill Hui-Kuo Shu Candace C. Fleischer
author_facet	Selin Ekici Benjamin B. Risk Stewart G. Neill Hui-Kuo Shu Candace C. Fleischer
author_sort	Selin Ekici
title	Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR
title_short	Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR
title_full	Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR
title_fullStr	Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR
title_full_unstemmed	Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR
title_sort	characterization of dysregulated glutamine metabolism in human glioma tissue with 1h nmr
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/fdcc5c2f91e24a72a68db8e571d3162b
work_keys_str_mv	AT selinekici characterizationofdysregulatedglutaminemetabolisminhumangliomatissuewith1hnmr AT benjaminbrisk characterizationofdysregulatedglutaminemetabolisminhumangliomatissuewith1hnmr AT stewartgneill characterizationofdysregulatedglutaminemetabolisminhumangliomatissuewith1hnmr AT huikuoshu characterizationofdysregulatedglutaminemetabolisminhumangliomatissuewith1hnmr AT candacecfleischer characterizationofdysregulatedglutaminemetabolisminhumangliomatissuewith1hnmr
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Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR

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