Evaluation of complement proteins as screening markers for colorectal cancer

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Lack of symptoms results in late detection and increased mortality. Inflammation, including complement activation, plays an important role in tumorigenesis.

EXPERIMENTAL DESIGN: The concentrations of nine proteins of the lectin pathway of the complement system were determined using time-resolved immunofluorometric assays. The first cohort investigated comprised a matched case-control study of 95 patients with CRC, 48 patients with adenomas and 48 individuals without neoplastic findings. Based on the results, Collectin-liver 1 (CL-L1), M-ficolin and MAp44 were determined as the most promising biomarkers and were subsequently evaluated in a case-control study of 99 CRC patients, 196 patients with adenomas and 696 individuals without neoplastic bowel lesions.

RESULTS: Using logistic regression, we found that CL-L1, M-ficolin and MAp44 levels could significantly distinguish between patients with CRC, patients with adenomas and individuals without neoplastic bowel lesions. Higher levels of CL-L1 or MAp44 were associated with lower odds of CRC (OR 0.42 (0.25-0.70) p = 0.0003 and OR 0.39 (0.23-0.65) p = 0.0003, respectively), whereas higher levels of M-ficolin were associated with higher odds of CRC compared to individuals without CRC (OR 1.94 (1.46-2.59) p < 0.0001). The combination of CL-L1, M-ficolin and MAp44 in a test of CRC versus individuals without CRC resulted in 36 % sensitivity at 83 % specificity.

CONCLUSION: CL-L1, M-ficolin and MAp44 in combination discriminate between CRC and patients without cancer. The markers did not have sufficient discriminatory value for CRC detection, but may prove useful for screening when combined with other markers.