Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia
BackgroundCachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is know...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1286896/full |
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| author | Tushar H. More Karsten Hiller Martin Seifert Martin Seifert Thomas Illig Thomas Illig Rudi Schmidt Rudi Schmidt Raphael Gronauer Raphael Gronauer Thomas von Hahn Thomas von Hahn Thomas von Hahn Hauke Weilert Hauke Weilert Hauke Weilert Axel Stang Axel Stang Axel Stang |
| author_facet | Tushar H. More Karsten Hiller Martin Seifert Martin Seifert Thomas Illig Thomas Illig Rudi Schmidt Rudi Schmidt Raphael Gronauer Raphael Gronauer Thomas von Hahn Thomas von Hahn Thomas von Hahn Hauke Weilert Hauke Weilert Hauke Weilert Axel Stang Axel Stang Axel Stang |
| author_sort | Tushar H. More |
| collection | DOAJ |
| description | BackgroundCachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit.MethodsSerum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis.ResultsComparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways.ConclusionWe found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care. |
| first_indexed | 2024-03-07T23:16:03Z |
| format | Article |
| id | doaj.art-877b087badc74524b315595bfa9f72aa |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-07T23:16:03Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-877b087badc74524b315595bfa9f72aa2024-02-21T11:20:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-02-011410.3389/fonc.2024.12868961286896Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexiaTushar H. More0Karsten Hiller1Martin Seifert2Martin Seifert3Thomas Illig4Thomas Illig5Rudi Schmidt6Rudi Schmidt7Raphael Gronauer8Raphael Gronauer9Thomas von Hahn10Thomas von Hahn11Thomas von Hahn12Hauke Weilert13Hauke Weilert14Hauke Weilert15Axel Stang16Axel Stang17Axel Stang18Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, GermanyDepartment of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, GermanyAsklepios Precision Medicine, Asklepios Hospitals GmbH & Co KgaA, Königstein (Taunus), GermanyConnexome GmbH, Fischen, GermanyDepartment of Human Genetics, Hannover Medical School, Hannover, GermanyHannover Unified Biobank (HUB), Hannover, GermanyAsklepios Precision Medicine, Asklepios Hospitals GmbH & Co KgaA, Königstein (Taunus), GermanyImmunetrue, Cologne, GermanyAsklepios Precision Medicine, Asklepios Hospitals GmbH & Co KgaA, Königstein (Taunus), GermanyConnexome GmbH, Fischen, GermanyAsklepios Hospital Barmbek, Department of Gastroenterology, Hepatology and Endoscopy, Hamburg, GermanyAsklepios Tumorzentrum Hamburg, Hamburg, GermanySemmelweis University, Asklepios Campus Hamburg, Budapest, HungaryAsklepios Tumorzentrum Hamburg, Hamburg, GermanySemmelweis University, Asklepios Campus Hamburg, Budapest, Hungary0Asklepios Hospital Barmbek, Department of Hematology, Oncology and Palliative Care Medicine, Hamburg, GermanyAsklepios Tumorzentrum Hamburg, Hamburg, GermanySemmelweis University, Asklepios Campus Hamburg, Budapest, Hungary0Asklepios Hospital Barmbek, Department of Hematology, Oncology and Palliative Care Medicine, Hamburg, GermanyBackgroundCachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit.MethodsSerum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis.ResultsComparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways.ConclusionWe found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.https://www.frontiersin.org/articles/10.3389/fonc.2024.1286896/fullcancer cachexiaGC-MS metabolomicserythronic acidglucuronic acidserum metabolitesmetabolic pathways |
| spellingShingle | Tushar H. More Karsten Hiller Martin Seifert Martin Seifert Thomas Illig Thomas Illig Rudi Schmidt Rudi Schmidt Raphael Gronauer Raphael Gronauer Thomas von Hahn Thomas von Hahn Thomas von Hahn Hauke Weilert Hauke Weilert Hauke Weilert Axel Stang Axel Stang Axel Stang Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia Frontiers in Oncology cancer cachexia GC-MS metabolomics erythronic acid glucuronic acid serum metabolites metabolic pathways |
| title | Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia |
| title_full | Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia |
| title_fullStr | Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia |
| title_full_unstemmed | Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia |
| title_short | Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia |
| title_sort | metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia |
| topic | cancer cachexia GC-MS metabolomics erythronic acid glucuronic acid serum metabolites metabolic pathways |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1286896/full |
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