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Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium

  • Anne J.M.R. Geijsen
  • , Eline H. van Roekel
  • , Fränzel J.B. van Duijnhoven
  • , David Achaintre
  • , Thomas Bachleitner-Hofmann
  • , Andreas Baierl
  • , Michael M. Bergmann
  • , Jürgen Boehm
  • , Martijn J.L. Bours
  • , Hermann Brenner
  • , Stéphanie O. Breukink
  • , Stefanie Brezina
  • , Jenny Chang-Claude
  • , Esther Herpel
  • , Johannes H.W. de Wilt
  • , Audrey Gicquiau
  • , Biljana Gigic
  • , Tanja Gumpenberger
  • , Bibi M.E. Hansson
  • , Michael Hoffmeister
    • Andreana N. Holowatyj, Judith Karner-Hanusch, Pekka Keski-Rahkonen, Eric T.P. Keulen, Janna L. Koole, Gernot Leeb, Jennifer Ose, Peter Schirmacher, Martin A. Schneider, Petra Schrotz-King, Anton Stift, Arve Ulvik, F. Jeroen Vogelaar, Evertine Wesselink, Moniek van Zutphen, Andrea Gsur, Nina Habermann, Ellen Kampman, Augustin Scalbert, Per M. Ueland, Alexis B. Ulrich, Cornelia M. Ulrich, Matty P. Weijenberg, Dieuwertje E. Kok

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I–IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I–IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (pFDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (pFDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.
Original languageEnglish
Pages (from-to)3256-3266
JournalInternational Journal of Cancer
Volume146
Issue number12
DOIs
Publication statusPublished - 15 Jun 2020
Externally publishedYes

Funding

The authors would like to acknowledge the contribution of all COLON, EnCoRe, ColoCare and CORSA participants. COLON study: The authors would like to thank the COLON investigators at Wageningen University & Research and the involved clinicians in the participating hospitals. EnCoRe study: The authors would like to thank all participants of the EnCoRe study and the health professionals in the three hospitals involved in the recruitment of participants of the study: Maastricht University Medical Center+, VieCuri Medical Center and Zuyderland Medical Center. The authors would also like to thank the MEMIC center for data and information management for facilitating the logistic processes and data management of our study. Finally, the authors would like to thank the research dieticians and research assistant who are responsible for patient inclusion and follow‐up, performing home visits, as well as data collection and processing. ColoCare Study: ColoCare samples were stored by the liquid biobank of the National Center for Tumor Diseases according to the SOPs of the Biomaterialbank Heidelberg. Lin Zielske, Anett Brendel, Renate Skatula, Marita Wenzel supported biobanking at the National Center for Tumor Diseases. In addition, the authors would like to thank Rifraz Farook and Werner Diehl for their data management support and the ColoCare team, specifically Torsten Kölsch, Clare Abbenhardt‐Martin, Susanne Jakob and Judith Kammer for patient recruitment and follow‐up. CORSA: The authors kindly thank Michael Micksche (Institute of Cancer Research, Department of Medicine I, Medical University of Vienna), Karl Mach, Azita Deutinger‐Permoon (KRAGES, Austria) and their coworkers for supporting CORSA recruitment. In addition, the authors would like to acknowledge Elisabeth Feik, Philipp Hofer and Cornelia Zöchmeister, for patient recruitment, sample processing and follow‐up. A.N.H. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32 HG008962 from the National Human Genome Research Institute. E.H.v.R. was financially supported by Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program (grant number 2016/1620). J.L.K. was supported by Kankeronderzoekfonds Limburg as part of Health Foundation Limburg (grant number 00005739). The authors would like to acknowledge the contribution of all COLON, EnCoRe, ColoCare and CORSA participants. COLON study: The authors would like to thank the COLON investigators at Wageningen University & Research and the involved clinicians in the participating hospitals. EnCoRe study: The authors would like to thank all participants of the EnCoRe study and the health professionals in the three hospitals involved in the recruitment of participants of the study: Maastricht University Medical Center+, VieCuri Medical Center and Zuyderland Medical Center. The authors would also like to thank the MEMIC center for data and information management for facilitating the logistic processes and data management of our study. Finally, the authors would like to thank the research dieticians and research assistant who are responsible for patient inclusion and follow-up, performing home visits, as well as data collection and processing. ColoCare Study: ColoCare samples were stored by the liquid biobank of the National Center for Tumor Diseases according to the SOPs of the Biomaterialbank Heidelberg. Lin Zielske, Anett Brendel, Renate Skatula, Marita Wenzel supported biobanking at the National Center for Tumor Diseases. In addition, the authors would like to thank Rifraz Farook and Werner Diehl for their data management support and the ColoCare team, specifically Torsten Kölsch, Clare Abbenhardt-Martin, Susanne Jakob and Judith Kammer for patient recruitment and follow-up. CORSA: The authors kindly thank Michael Micksche (Institute of Cancer Research, Department of Medicine I, Medical University of Vienna), Karl Mach, Azita Deutinger-Permoon (KRAGES, Austria) and their coworkers for supporting CORSA recruitment. In addition, the authors would like to acknowledge Elisabeth Feik, Philipp Hofer and Cornelia Zöchmeister, for patient recruitment, sample processing and follow-up. A.N.H. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32 HG008962 from the National Human Genome Research Institute. E.H.v.R. was financially supported by Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program (grant number 2016/1620). J.L.K. was supported by Kankeronderzoekfonds Limburg as part of Health Foundation Limburg (grant number 00005739).

FundersFunder number
Biomaterialbank Heidelberg
ColoCare
Health Foundation Limburg
National Center for Tumor Diseases
VieCuri Medical Center
Zuyderland Medical Center
National Institutes of Health
National Human Genome Research InstituteT32HG008962
World Cancer Research Fund International00005739
World Cancer Research Fund2016/1620
Medizinische Universität Wien
Wereld Kanker Onderzoek Fonds

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