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Open AccessArticle

Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study

1
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
2
Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
3
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69117 Heidelberg, Germany
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Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69117 Heidelberg, Germany
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Diagnostic and Interventional Radiology, University of Heidelberg, 69117 Heidelberg, Germany
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Institute of Medical Biometry and Informatics, University of Heidelberg, 69117 Heidelberg, Germany
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European Molecular Biology Laboratory (EMBL), Genome Biology, 69117 Heidelberg, Germany
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Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14260, USA
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Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
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Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA
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Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Department of Surgery, Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO 63110, USA
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Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(9), 178; https://doi.org/10.3390/metabo9090178
Received: 16 July 2019 / Revised: 26 August 2019 / Accepted: 4 September 2019 / Published: 6 September 2019
(This article belongs to the Special Issue Metabolomics in Epidemiological Studies)
Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary metabolic profiles in newly diagnosed colorectal cancer patients (stage I–IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (n = 16), pre-cachectic (n = 13), or non-cachectic (n = 23) based on standard criteria on weight loss over time at two time points. Urine samples were collected pre-surgery, and 6 and 12 months thereafter. Fat and muscle mass area were assessed utilizing computed tomography scans at the time of surgery. N = 152 compounds were detected using untargeted metabolomics with gas chromatography–mass spectrometry and n = 154 features with proton nuclear magnetic resonance spectroscopy. Thirty-four metabolites were overlapping across platforms. We calculated differences across groups and performed discriminant and overrepresentation enrichment analysis. We observed a trend for 32 compounds that were nominally significantly different across groups, although not statistically significant after adjustment for multiple testing. Nineteen compounds could be identified, including acetone, hydroquinone, and glycine. Comparing cachectic to non-cachectic patients, higher levels of metabolites such as acetone (Fold change (FC) = 3.17; p = 0.02) and arginine (FC = 0.33; p = 0.04) were observed. The two top pathways identified were glycerol phosphate shuttle metabolism and glycine and serine metabolism pathways. Larger subsequent studies are needed to replicate and validate these results. View Full-Text
Keywords: cancer cachexia; metabolomics; serial samples; urinary profiles; colorectal cancer cancer cachexia; metabolomics; serial samples; urinary profiles; colorectal cancer
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Ose, J.; Gigic, B.; Lin, T.; Liesenfeld, D.B.; Böhm, J.; Nattenmüller, J.; Scherer, D.; Zielske, L.; Schrotz-King, P.; Habermann, N.; Ochs-Balcom, H.M.; Peoples, A.R.; Hardikar, S.; Li, C.I.; Shibata, D.; Figueiredo, J.; Toriola, A.T.; Siegel, E.M.; Schmit, S.; Schneider, M.; Ulrich, A.; Kauczor, H.-U.; Ulrich, C.M. Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study. Metabolites 2019, 9, 178.

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