Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets

dc.bibliographicCitation.firstPage1564
dc.bibliographicCitation.issue6
dc.bibliographicCitation.volume14
dc.contributor.authorAlwahsh, Mohammad
dc.contributor.authorKnitsch, Robert
dc.contributor.authorMarchan, Rosemarie
dc.contributor.authorLambert, Jörg
dc.contributor.authorHoerner, Christian
dc.contributor.authorZhang, Xiaonan
dc.contributor.authorSchalke, Berthold
dc.contributor.authorLee, De-Hyung
dc.contributor.authorBulut, Elena
dc.contributor.authorGraeter, Thomas
dc.contributor.authorOtt, German
dc.contributor.authorKurz, Katrin S.
dc.contributor.authorPreissler, Gerhard
dc.contributor.authorSchölch, Sebastian
dc.contributor.authorFarhat, Joviana
dc.contributor.authorYao, Zhihan
dc.contributor.authorSticht, Carsten
dc.contributor.authorStröbel, Philipp
dc.contributor.authorHergenröder, Roland
dc.contributor.authorMarx, Alexander
dc.contributor.authorBelharazem, Djeda
dc.date.accessioned2023-04-03T04:38:33Z
dc.date.available2023-04-03T04:38:33Z
dc.date.issued2022
dc.description.abstractThymomas and thymic carcinomas (TC) are malignant thymic epithelial tumors (TETs) with poor outcome, if non-resectable. Metabolic signatures of TETs have not yet been studied and may offer new therapeutic options. Metabolic profiles of snap-frozen thymomas (WHO types A, AB, B1, B2, B3, n = 12) and TCs (n = 3) were determined by high resolution magic angle spinning 1H nuclear magnetic resonance (HRMAS 1H-NMR) spectroscopy. Metabolite-based prediction of active KEGG metabolic pathways was achieved with MetPA. In relation to metabolite-based metabolic pathways, gene expression signatures of TETs (n = 115) were investigated in the public “The Cancer Genome Atlas” (TCGA) dataset using gene set enrichment analysis. Overall, thirty-seven metabolites were quantified in TETs, including acetylcholine that was not previously detected in other nonendocrine cancers. Metabolite-based cluster analysis distinguished clinically indolent (A, AB, B1) and aggressive TETs (B2, B3, TCs). Using MetPA, six KEGG metabolic pathways were predicted to be activated, including proline/arginine, glycolysis and glutathione pathways. The activated pathways as predicted by metabolite-profiling were generally enriched transcriptionally in the independent TCGA dataset. Shared high lactic acid and glutamine levels, together with associated gene expression signatures suggested a strong “Warburg effect”, glutaminolysis and redox homeostasis as potential vulnerabilities that need validation in a large, independent cohort of aggressive TETs. If confirmed, targeting metabolic pathways may eventually prove as adjunct therapeutic options in TETs, since the metabolic features identified here are known to confer resistance to cisplatin-based chemotherapy, kinase inhibitors and immune checkpoint blockers, i.e., currently used therapies for non-resectable TETs.eng
dc.description.sponsorshipLeibniz_Fonds
dc.description.versionpublishedVersioneng
dc.identifier.urihttps://oa.tib.eu/renate/handle/123456789/11836
dc.identifier.urihttp://dx.doi.org/10.34657/10869
dc.language.isoeng
dc.publisherBasel : MDPI
dc.relation.doihttps://doi.org/10.3390/cancers14061564
dc.relation.essn2072-6694
dc.relation.ispartofseriesCancers 14 (2022), Nr. 6
dc.rights.licenseCC BY 4.0 Unported
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectBiomarkereng
dc.subjectHRMAS H-NMR 1eng
dc.subjectMetabolomicseng
dc.subjectThymic carcinomaeng
dc.subjectThymomaeng
dc.subject.ddc610
dc.titleMetabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targetseng
dc.typearticle
dc.typeText
dcterms.bibliographicCitation.journalTitleCancers
tib.accessRightsopenAccess
wgl.contributorISAS
wgl.subjectMedizin, Gesundheitger
wgl.typeZeitschriftenartikelger
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