Abstract 5325: Associations between adipose tissue compartments and the plasma metabolome in colorectal cancer patients: Results from the ColoCare Study
Authors: Jennifer Ose, Tengda Lin, Nina Habermann, David Achaintre, Pekka Keski-Rahkonen, Augustin Scalbert, Juergen Boehm, Biljana Gigic, Dominique Scherer, Johanna Nattenmueller, Mariam Salou, Lin Zielske, Alexis Ulrich, Jewel Samadder, Hanno Glimm, Stephen Hursting, Hans-Ulrich Kauczor, Cornelia M. Ulrich
Journal: Cancer Research (2017)

Abstract BACKGROUND Obesity is associated with colorectal cancer (CRC) risk and prognosis. We investigated associations between plasma metabolites and multiple dimensions of body fatness in early- and late-stage CRC patients enrolled in the ColoCare Study, a multicenter international cohort. METHODS Pre-operatively collected plasma samples of newly diagnosed CRC patients [n=212; (stage I-IV)] from the ColoCare Study were utilized to perform targeted metabolomics by mass spectrometry using the AbsoluteIDQ p180 Kit assay (Biocrates; intra-plate CVs &amp;lt;20%, inter-plate CVs &amp;lt;20%) as part of the MetaboCCC consortium. Abdominal adipose tissue (AT) was assessed by area-based quantification of visceral (VAT), and subcutaneous AT (SAT), as well as their ratio (VAT:SAT) on levels L3/L4 and L4/L5. Body mass index (BMI) was calculated (kg/m2). Demographic and clinical data were abstracted from medical records. Partial correlations and regression analyses were used, adjusting for age, sex, batch, stage overall and in stratified analyses by early- (I/II; n=111) and late-stage (III/IV; n=101) and corrected for multiple hypotheses testing (FDR). We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up. RESULTS A total of 127 metabolites from 5 different compound classes (i.e., amino acids, biogenic amines, glycerophospholipids, sphingomyelins, acylcarnitines) were included for statistical analysis. Overall obesity (BMI) and VAT were not associated with any metabolites in early-stage or late-stage tumors. SAT (L3/L4 and L4/L5) was inversely associated with 3 glycerophospholipids in analyses restricted to late-stage, but not early-stage tumors: PC-ae-C34_0 (pFDR=0.02), PC-ae-C36_0 (pFDR=0.03), PC-ae-C36_1 (pFDR=0.03). A doubling of concentration in selected glycerophospholipids was associated with a significant increase in risk for death in late-stage (III and IV) CRC. CONCLUSIONS We observed a negative association between subcutaneous abdominal adiposity and glycerophospholipids in late-stage CRC. Glycerophospholipids are major components of cellular membranes and are pertinent to cancer cells that undergo progression and metastasis. Our results suggest that a metabolic shift in glycerophospholipid metabolism in late-stage tumors may take place and have potential impact on survival. Note: This abstract was not presented at the meeting. Citation Format: Jennifer Ose, Tengda Lin, Nina Habermann, David Achaintre, Pekka Keski-Rahkonen, Augustin Scalbert, Juergen Boehm, Biljana Gigic, Dominique Scherer, Johanna Nattenmueller, Mariam Salou, Lin Zielske, Alexis Ulrich, Jewel Samadder, Hanno Glimm, Stephen Hursting, Hans-Ulrich Kauczor, Cornelia M. Ulrich. Associations between adipose tissue compartments and the plasma metabolome in colorectal cancer patients: Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5325. doi:10.1158/1538-7445.AM2017-5325