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Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare)

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Abstract

Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). We aimed to determine changes in the metabolome of the longer clinical follow-up and ascertain candidate markers with possibly prognostic significance. In total, 199 urine samples from CRC patients prior to surgery (n = 97) or 1–8 days post-surgery (n = 12), and then after 6 (n = 52) and 12 months (n = 38) were analyzed using both GC–MS and 1H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed. Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC. We were able to differentiate the metabolite profiles of pre-surgery CRC patients from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC = 0.89; 95 % CI 0.84–0.95). This is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case–control studies and metabolites which may represent prognostic biomarker candidates of CRC.

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Acknowledgments

The ColoCare study has been funded by the German Consortium for Translational Cancer Research (DKTK), Matthias Lackas Foundation and the Helmholtz International Graduate School for Cancer Research, Heidelberg. We thank our collaborators, in particular Prof. Hermann Brenner, Prof. Jenny Chang-Claude and Dr. Michael Hoffmeister. We also thank all the study staff who through their energy and effort have made this study possible, particularly Dr. Clare Abbenhardt, Dr. Stephanie Zschäbitz, Thorsten Kölsch, Judith Kammer, Stephanie Tosic, Verena Widmer, Manja Ghajar Rahimi, Biljana Gigic, Werner Diehl, Rifraz Farook and many others. Last, we are truly grateful for the time and cooperation of our study participants.

Conflict of interest

The authors declare that there are no conflicts of interest.

Compliance with ethical requirements

The ColoCare study has been approved by the ethics committee of the medical faculty at the University of Heidelberg and study participants provided their written informed consent.

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Authors and Affiliations

  1. Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany

    David B. Liesenfeld, Nina Habermann, Reka Toth, Robert W. Owen, Eva Frei, Jürgen Böhm, Petra Schrotz-King & Cornelia M. Ulrich

  2. Genomics and Proteomics Core Facility, Molecular Structure Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Karel D. Klika

  3. Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, USA

    Cornelia M. Ulrich

  4. German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany

    David B. Liesenfeld, Nina Habermann, Reka Toth, Robert W. Owen, Eva Frei, Jürgen Böhm, Petra Schrotz-King & Cornelia M. Ulrich

  5. Population Sciences, Huntsman Cancer Institute, Salt Lake City, Utah, USA

    Cornelia M. Ulrich

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  1. David B. Liesenfeld
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  2. Nina Habermann
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  3. Reka Toth
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  4. Robert W. Owen
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  9. Cornelia M. Ulrich
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Correspondence to Cornelia M. Ulrich.

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Liesenfeld, D.B., Habermann, N., Toth, R. et al. Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare). Metabolomics 11, 998–1012 (2015). https://doi.org/10.1007/s11306-014-0758-3

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