Universität zu Köln

Trautwein, Christoph, Zizmare, Laimdota ORCID: 0000-0001-7208-3659, Maurer, Irina, Bender, Benjamin, Bayer, Bjorn, Ernemann, Ulrike, Tatagiba, Marcos, Grau, Stefan J., Pichler, Bernd J., Skardelly, Marco ORCID: 0000-0002-3870-6872 and Tabatabai, Ghazaleh (2022). Tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and treatment. JCI Insight, 7 (3). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

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Abstract

The discovery of the oncometabolite 2-hydroxyglutarate in isocitrate dehydrogenase 1-mutated (IDH1-mutated) tumor entities affirmed the role of metabolism in cancer. However, large databases with tissue metabolites that are modulated by IDH1 mutation remain an area of development. Here, we present an unprecedented and valuable resource for tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and tumor treatments in 101 tissue samples from 73 diffuse glioma patients (24 astrocytoma, 17 oligodendroglioma, 32 glioblastoma), investigated by NMR-based metabolomics and supported by RNA-Seq. We discovered comparison-specific metabolites and pathways modulated by IDH1(IDH1 mutation status cohort) and tumor entity. The Longitudinal investigation cohort provides metabolic profiles of untreated and corresponding treated glioma samples at first progression. Most interestingly, univariate and multivariate cox regressions and Kaplan-Meier analyses revealed that tissue metabolites correlate with progression-free and overall survival. Thus, this study introduces potentially novel candidate prognostic and surrogate metabolite biomarkers for future prospective clinical studies, aiming at further refining patient stratification in diffuse glioma. Furthermore, our data will facilitate the generation of so-far-unanticipated hypotheses for experimental studies to advance our molecular understanding of glioma biology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Trautwein, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Zizmare, Laimdota UNSPECIFIED orcid.org/0000-0001-7208-3659 UNSPECIFIED Maurer, Irina UNSPECIFIED UNSPECIFIED UNSPECIFIED Bender, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Bayer, Bjorn UNSPECIFIED UNSPECIFIED UNSPECIFIED Ernemann, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Tatagiba, Marcos UNSPECIFIED UNSPECIFIED UNSPECIFIED Grau, Stefan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pichler, Bernd J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Skardelly, Marco UNSPECIFIED orcid.org/0000-0002-3870-6872 UNSPECIFIED Tabatabai, Ghazaleh UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-682715
DOI:	10.1172/jci.insight.153526
Journal or Publication Title:	JCI Insight
Volume:	7
Number:	3
Date:	2022
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	2379-3708
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CENTRAL-NERVOUS-SYSTEM; ATP CITRATE LYASE; CLASSIFICATION; CANCER; TUMORS Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68271