Association of angiopoietin-2, C-reactive protein and markers of obesity and insulin resistance with survival outcome in colorectal cancer

Abstract

Background:This study investigated the relationship of obesity, insulin resistance, inflammation and angiogenesis with cancer progression and survival in a colorectal cancer cohort.Methods:Clinical and pathological data, along with anthropometric and follow-up data, were collected from 344 consecutive colorectal cancer patients. Serum samples at diagnosis were analysed by immunoassay for adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide.Results:Serum Ang-2 and VEGF-A levels increased with tumour T stage (P=0.007 and P=0.025, respectively) and N stage (P=0.02 and P=0.03, respectively), and correlated with CRP levels (r=0.43, P<0.001 and r=0.23, P<0.001, respectively). Angiopoietin-2 correlated with C-peptide (r=0.14, P=0.007) and VEGF-A with IGF-1 in males (r=0.25, P=0.001). Kaplan–Meier analysis showed that patients with high serum levels of CRP and Ang-2 had significantly reduced survival (both P⩽0.001). After adjusting for tumour stage and age, Ang-2 remained a significant predictor of survival. The CRP levels were inversely associated with survival in American Joint Committee on Cancer stage II patients (P=0.038), suggesting that CRP could be used to support treatment decisions in this subgroup. Serum markers and anthropometric measures of obesity correlated with each other, but not with survival.Conclusion:Our study supports the concept that obesity-related inflammation, rather than obesity itself, is associated with colorectal cancer progression and survival. The study confirms serum Ang-2 as a predictive marker for outcome of colorectal cancer.

Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

“…In line with this hypothesis, the production of Ang-2 within the tumor microenvironment could depend on VEGF (44). Moreover, Ang-2 expression was shown to be correlated with colorectal cancer stages and progression (44,45). Nevertheless the precise role of Ang-2 cancer progression needs to be further clarified.…”

Association of obesity and overweight with overall survival in colorectal cancer patients: a meta-analysis of 29 studies

“…The main characteristics of the 29 included studies are summarized in Table 1. Of the included studies, 14 were conducted in North America [11,12,21,22,24,25,28,32,34,37,38,41,42,44], five were conducted in Europe [14,26,27,30,40], six were conducted in Asia [15,23,31,33,35,36], three were conducted in Oceania [13,29,43], and one study included multiple cohorts from North America and Europe [39].…”

Microparticles in Angiogenesis

“…32 Elevated levels of proangiogenic factors have been detected in cancer patients and a negative correlation has been reported between the levels of proangiogenic factors and their poor outcome. 33,34 For instance, circulating levels of soluble VEGF receptor-1 are increased in hepatocellular carcinoma and are associated with poor survival in these patients. 35 Also, patients with breast cancer have higher plasma VEGF and angiogenin levels than control subjects; 36 and in metastatic gastric patients, VEGF and regulated-on-activation normal T-cell-expressed and secreted levels correlate with the severity of the metastasis.…”