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

  1. Alwahsh, Mohammad
  2. Knitsch, Robert
  3. Marchan, Rosemarie ORCID logo
  4. Lambert, Jörg
  5. Hoerner, Christian
  6. Zhang, Xiaonan ORCID logo
  7. Schalke, Berthold
  8. Lee, De-Hyung
  9. Bulut, Elena
  10. Graeter, Thomas
  11. Ott, German
  12. Kurz, Katrin S.
  13. Preissler, Gerhard
  14. Schölch, Sebastian ORCID logo
  15. Farhat, Joviana
  16. Yao, ZhiHan
  17. Sticht, Carsten
  18. Ströbel, Philipp
  19. Hergenröder, Roland
  20. Marx, Alexander ORCID logo
  21. Belharazem, Djeda

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1000 Titel
  • Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets
1000 Autor/in
  1. Alwahsh, Mohammad |
  2. Knitsch, Robert |
  3. Marchan, Rosemarie |
  4. Lambert, Jörg |
  5. Hoerner, Christian |
  6. Zhang, Xiaonan |
  7. Schalke, Berthold |
  8. Lee, De-Hyung |
  9. Bulut, Elena |
  10. Graeter, Thomas |
  11. Ott, German |
  12. Kurz, Katrin S. |
  13. Preissler, Gerhard |
  14. Schölch, Sebastian |
  15. Farhat, Joviana |
  16. Yao, ZhiHan |
  17. Sticht, Carsten |
  18. Ströbel, Philipp |
  19. Hergenröder, Roland |
  20. Marx, Alexander |
  21. Belharazem, Djeda |
1000 Erscheinungsjahr 2022
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-03-18
1000 Erschienen in
1000 Quellenangabe
  • 14(6):1564
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3390/cancers14061564 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945961/ |
1000 Ergänzendes Material
  • https://www.mdpi.com/2072-6694/14/6/1564#supplementary |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Thymomas 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 non-endocrine 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.
1000 Sacherschließung
lokal biomarker
lokal metabolomics
lokal HRMAS 1H-NMR
lokal thymic carcinoma
lokal thymoma
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/QWx3YWhzaCwgTW9oYW1tYWQ=|https://frl.publisso.de/adhoc/uri/S25pdHNjaCwgUm9iZXJ0|https://orcid.org/0000-0003-4414-1633|https://frl.publisso.de/adhoc/uri/TGFtYmVydCwgSsO2cmc=|https://frl.publisso.de/adhoc/uri/SG9lcm5lciwgQ2hyaXN0aWFu|https://orcid.org/0000-0003-4040-1784|https://frl.publisso.de/adhoc/uri/U2NoYWxrZSwgQmVydGhvbGQ=|https://frl.publisso.de/adhoc/uri/TGVlLCBEZS1IeXVuZw==|https://frl.publisso.de/adhoc/uri/QnVsdXQsIEVsZW5h|https://frl.publisso.de/adhoc/uri/R3JhZXRlciwgVGhvbWFz|https://frl.publisso.de/adhoc/uri/T3R0LCBHZXJtYW4g|https://frl.publisso.de/adhoc/uri/S3VyeiwgS2F0cmluIFMu|https://frl.publisso.de/adhoc/uri/UHJlaXNzbGVyLCBHZXJoYXJk|https://orcid.org/0000-0003-0012-3177|https://frl.publisso.de/adhoc/uri/RmFyaGF0LCBKb3ZpYW5h|https://frl.publisso.de/adhoc/uri/WWFvLCBaaGlIYW4=|https://frl.publisso.de/adhoc/uri/U3RpY2h0LCBDYXJzdGVu|https://frl.publisso.de/adhoc/uri/U3Ryw7ZiZWwsIFBoaWxpcHA=|https://frl.publisso.de/adhoc/uri/SGVyZ2VucsO2ZGVyLCBSb2xhbmQ=|https://orcid.org/0000-0001-9722-2483|https://frl.publisso.de/adhoc/uri/QmVsaGFyYXplbSwgRGplZGE=
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  1. Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen |
  2. Regierender Bürgermeister von Berlin |
  3. Senatskanzlei Wissenschaft und Forschung |
  4. Bundesministerium für Bildung und Forschung |
  5. Leibniz-Gemeinschaft |
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    1000 Förderer Regierender Bürgermeister von Berlin |
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