Background: Adiposity has been linked to both risk and prognosis of colorectal cancer; however, the impact of different compartments of adipose tissue (visceral vs. subcutaneous) is unclear. In healthy individuals, adiposity is associated with elevated biomarkers of inflammation, which provides a mechanistic link between adiposity and cancer risk. For prognosis, the downstream effects of inflammation on angiogenesis may be central. We investigated associations between adiposity and biomarkers of inflammation, as well as angiogenesis, in colorectal cancer patients enrolled in the ColoCare Study, an international multicenter patient cohort.
Methods: We utilized preoperatively obtained serum samples of patients with newly diagnosed colorectal cancer [n=164; (stage I-IV)] from the ColoCare Study in Heidelberg, Germany, with available diagnostic multi-detector-CT images for adipose tissue quantification. Abdominal adipose tissue was assessed by area-based quantification of visceral (VAT), and subcutaneous adipose tissue (SAT), as well as their ratio (VAT/SAT) on levels L3/L4 and L4/L5. Body mass index (BMI) was calculated (kg/m2) and demographic and clinical-surgical data were abstracted from medical records. Circulating CRP, SAA, VEGF-A, VEGF-D, sICAM-1 and sVCAM-1 levels were assessed on the Meso Scale Discoveries platform with V-plex assays at the Huntsman Cancer Institute (average intra-plate CVs 2.9%, inter-plate CVs 7.9%). Partial correlations and regression analyses, adjusting for age, sex and tumor stage were performed.
Results: While overall obesity (BMI) was only significantly associated with sVCAM (r=0.23, p=0.006), visceral adiposity (VAT) was associated with both CRP and SAA (r=0.21, p=0.01 and r=0.17, p=0.04, respectively). There was no association between SAT and the measured biomarkers. Most predictive was the ratio of VAT/SAT on level L3/L4, which was associated with CRP (r=0.18, p=0.04), SAA (r=0.24, p=0.006), sICAM-1 (r=0.18, p=0.04), and particularly VEGF-A (r=0.28, p=0.0008). Similar associations were observed for the VAT/SAT ratio on level L4/5.
Conclusions: We demonstrated a link between specifically visceral adiposity and biomarkers of inflammation in colorectal cancer patients. In addition, we showed that visceral adiposity also affects circulating VEGF-A levels. This protein has various effects, including the induction of angiogenesis, vasculogenesis and endothelial cell growth, as well as the promotion of cell migration, and the inhibition of apoptosis. Our findings support a mechanistic role of visceral adipose tissue in colorectal cancer risk and potentially prognosis.
Citation Format: Cornelia M. Ulrich, Jürgen Böhm, Christy Warby, Tengda Lin, Mariam Salou, Biljana Gigic, Dominique Scherer, Johanna Nattenmueller, Jennifer Ose, Lin Zielske, Petra Schrotz-King, Torsten Kölsch, Erin Siegel, Christopher Li, Alexis Ulrich, Hanno Glimm, Jewel Samadder, Stephen Hursting, Hans-Ulrich Kauczor. Body fatness and adipose tissue subtypes are associated with circulating biomarkers of inflammation and angiogenesis in colorectal cancer patients: The ColoCare Study. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A26.