Multiplatform Urinary Metabolomics Profiling to Discriminate Cachectic from Non-Cachectic Colorectal Cancer Patients: Pilot Results from the ColoCare Study
Jennifer Ose,
Biljana Gigic,
Tengda Lin,
David B. Liesenfeld,
Jürgen Böhm,
Johanna Nattenmüller,
Dominique Scherer,
Lin Zielske,
Petra Schrotz-King,
Nina Habermann,
Heather M. Ochs-Balcom,
Anita R. Peoples,
Sheetal Hardikar,
Christopher I. Li,
David Shibata,
Jane Figueiredo,
Adetunji T. Toriola,
Erin M. Siegel,
Stephanie Schmit,
Martin Schneider,
Alexis Ulrich,
Hans-Ulrich Kauczor,
Cornelia M. Ulrich
Affiliations
Jennifer Ose
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
Biljana Gigic
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69117 Heidelberg, Germany
Tengda Lin
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
David B. Liesenfeld
Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69117 Heidelberg, Germany
Jürgen Böhm
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
Johanna Nattenmüller
Diagnostic and Interventional Radiology, University of Heidelberg, 69117 Heidelberg, Germany
Dominique Scherer
Institute of Medical Biometry and Informatics, University of Heidelberg, 69117 Heidelberg, Germany
Lin Zielske
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69117 Heidelberg, Germany
Petra Schrotz-King
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69117 Heidelberg, Germany
Nina Habermann
European Molecular Biology Laboratory (EMBL), Genome Biology, 69117 Heidelberg, Germany
Heather M. Ochs-Balcom
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
Anita R. Peoples
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
Sheetal Hardikar
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
Christopher I. Li
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
David Shibata
Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Jane Figueiredo
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Adetunji T. Toriola
Department of Surgery, Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO 63110, USA
Erin M. Siegel
Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Stephanie Schmit
Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Martin Schneider
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69117 Heidelberg, Germany
Alexis Ulrich
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69117 Heidelberg, Germany
Hans-Ulrich Kauczor
Diagnostic and Interventional Radiology, University of Heidelberg, 69117 Heidelberg, Germany
Cornelia M. Ulrich
Huntsman Cancer Institute, Salt Lake City, UT 84112, USA
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.