Body Fatness, Adipose Tissue Compartments, and Biomarkers of Inflammation and Angiogenesis in Colorectal Cancer: The ColoCare Study

Background: Adiposity has been linked to both risk and prognosis of colorectal cancer; however, the impact of different fat areas [visceral (VFA) vs. subcutaneous fat area (SFA)] is unclear. We investigated associations between adiposity and biomarkers of inflammation and angiogenesis among patients with colorectal cancer. Methods: Preoperative serum samples and computed tomography scans were obtained from 188 patients diagnosed with primary invasive stage I-IV colorectal cancer enrolled in the ColoCare Study. Adiposity was assessed by area-based quantification of VFA, SFA, and VFA:SFA ratio on spinal levels L3/L4 and L4/L5. Circulating levels of inflammation (CRP, SAA, sICAM-1, sVCAM-1) and angiogenesis (VEGF-A, VEGF-D) were assessed from patient sera on the Meso-Scale-Discoveries platform. Partial correlations and regression analyses, adjusted for age, sex, and tumor stage, were performed. Results: VFA was moderately correlated with CRP and SAA (CRP: L3/L4 and L4/L5:r=0.21, p=0.01; SAA: L3/L4:r=0.17, p=0.04). The correlation between SFA and the measured biomarkers were weak (r≤0.13, not significant). The ratio of VFA:SFA at L3/L4 was moderately correlated with VEGF-A (r=0.28, p=0.0008), and SAA (r=0.24, p=0.006), and less so with CRP (r=0.18, p=0.04) and sICAM-1 (r=0.18, p=0.04). Similar correlations were found for VFA:SFA ratio at L4/L5. Conclusions: We observed an association between visceral adiposity and biomarkers of inflammation and angiogenesis in colorectal cancer patients. In particular, the VFA:SFA ratio was correlated with circulating levels of pro-angiogenic biomarker VEGF-A. Impact: Our findings support a direct association of visceral adipose tissue with inflammatory and angiogenic processes, which play fundamental roles in the development and progression of colorectal cancer.