Abstract 5325: Associations between adipose tissue compartments and the plasma metabolome in colorectal cancer patients: Results from the ColoCare Study

Abstract

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 <20%, inter-plate CVs <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