Metabolomics profiling of visceral and abdominal subcutaneous adipose tissue in colorectal cancer patients: results from the ColoCare study

Jennifer Ose*, Andreana N. Holowatyj, Johanna Nattenmueller, Biljana Gigic, Tengda Lin, Caroline Himbert, Nina Habermann, David Achaintre, Augustin Scalbert, Pekka Keski-Rahkonen, Jurgen Bohm, Petra Schrotz-King, Martin Schneider, Alexis Ulrich, Ellen Kampman, Matty Weijenberg, Andrea Gsur, Per-Magne Ueland, Hans-Ulrich Kauczor, Cornelia M. Ulrich*

*Corresponding author for this work

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Abstract

Purpose Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients. Methods Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival. Results In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: p(FDR) range 0.017-0.049; TFA: p(FDR) range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (p(het) range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; p(het) = 0.00044). Conclusion These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.

Original languageEnglish
Pages (from-to)723-735
Number of pages13
JournalCancer Causes & Control
Volume31
Issue number8
DOIs
Publication statusPublished - Aug 2020

Keywords

  • Colorectal cancer
  • Adipose tissue
  • Survival
  • Glycerophospholipids
  • BODY-MASS INDEX
  • BREAST-CANCER
  • METABOLITE PROFILES
  • TUMOR PROGRESSION
  • OBESITY PARADOX
  • FAT
  • ASSOCIATIONS
  • MORTALITY
  • METAANALYSIS
  • BIOMARKERS

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