Association between post-treatment circulating biomarkers of inflammation and survival among stage II–III colorectal cancer patients

Abstract

Background: Biomarker studies on colorectal cancer (CRC) prognosis are limited to pre-diagnostic or pre-operative measures. Post-treatment biomarkers are not well understood for their associations with CRC survival. Methods: We included 306 eligible incident stage II–III CRC cases from the population-based Seattle Colon Cancer Family Registry. Concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), adiponectin, and leptin were measured using post-treatment plasma samples. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CRC-specific mortality were calculated using Cox proportional hazard models. Results: Elevated levels of CRP, IL-6, MCP-1, and adiponectin were significantly associated with a higher risk of all-cause mortality within 10 years post blood draw with HRs (95% CI) of 1.32 (1.10–2.59), 2.72 (2.07–3.56), 1.97 (1.18–3.28) and 1.71 (1.14–2.58), respectively. IL-6 and adiponectin had a dose–response effect (Ptrend < 0.0001). For CRC-specific mortality, we observed positive associations for CRP (HR = 1.75, 95% CI: 1.2–2.56), IL-6 (HR = 5.02, 95% CI: 2.92–8.59), MCP-1 (HR = 3.78, 95% CI: 1.41–10.08), and adiponectin (HR = 3.16, 95% CI: 1.27–7.86), and inverse association for leptin (HR = 0.44, 95% CI: 0.29–0.68) within the first year of blood draw, whereas the association for IL-6 remained statistically significant over 10 years. Conclusion: Our results support the role of chronic inflammation in CRC progression and suggested several post-treatment inflammatory biomarkers, particularly IL-6, are promising prognostic markers for stage II–III CRC patients.