Surgery, Gastroenterology and Oncology

Background: A raised pre-treatment carcinoembryonic antigen (CEA) level is frequently observed in colorectal cancer patients with metastatic disease and is thought to be a reflection of disease burden. Additionally, there is a growing body of evidence highlighting the influence of a pro-inflammatory host-response on colorectal cancer progression. Proinflammatory cytokines IL-1 , IL-6, IL-8 and TNF have been implicated in this relationship through experimental and clinical studies. We set out to evaluate whether combining circulating inflammatory markers, such as these, with CEA improves upon the stagespecificity of CEA alone.

Methods: Sixty patients were enrolled prospectively at a single centre over a sixteen month period into three groups: control (n=19), stage II (n=22) and stage IV (n=19) colorectal cancer. Baseline levels of carcinoembryonic antigen (CEA) as well as plasma IL-1 , IL-6, IL-8 and TNF were compared across the groups. The ability of each marker to distinguish patients by disease status was evaluated using Receiver Operator Characteristic (ROC) curve and Chi-squared analysis.

Results: CEA, IL-6 and IL-8 increased significantly between the three groups. CEA and IL-8 were most effective in discriminating between stage II and stage IV disease groups. We found IL8-CEA score was more effective in discriminating between stage II and stage IV CRC (OR 10.3, 95% CI 1.1-92.2, p=0.01) compared with CEA alone (OR 5.4, 95% CI 1.3-27.8, p=0.01).

Conclusion: Combining IL-8 with CEA improved upon the stage-specificity of CEA alone. This suggests a potential value for combining circulating inflammatory biomarkers with CEA to accurately stage CRC.

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