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

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: pFDR range 0.017-0.049; TFA: pFDR 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 (phet 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; phet = 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.

Keywords: Adipose tissue; Colorectal cancer; Glycerophospholipids; Survival.

Conflict of interest statement

Disclosure: C.M.U. has as cancer center director oversight over research funded by several pharmaceutical companies, but has not received funding directly herself. The remaining authors declare no conflict of interest.

Figures

Figure 1.. Adjusted hazard of overall death for colorectal cancer patients (at two-year follow-up) by presence of metastasis.

Analyses were adjusted for age, sex, stage (non-metastatic tumors) and analytical batch. The black box indicates the hazard ratio (HR), with horizontal grey lines representing the bounds of the 95% confidence interval (95% CI). Non-metastatic includes stage I – III tumors and metastatic includes stage IV tumors.