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Serum Mannan-Binding Lectin-Associated Serine Protease 2 Levels in Colorectal Cancer: Relation to Recurrence and Mortality

¹ Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark; ² Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark; and ³ Danish Cancer Society, Copenhagen, Denmark

Requests for reprints: Henriette Ytting, Department of Surgical Gastroenterology 435, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. Phone: 45-36323181; Fax: 45-36323760; E-mail: ytting{at}dadlnet.dk.

Purpose: Mannan-binding lectin-associated serine protease 2 (MASP-2) is a plasma protein involved in inflammatory processes. MASP-2 circulates in complex with the protein mannan-binding lectin (MBL) or ficolins, and is activated to recruit the complement system when MBL binds to its targets. The level of MASP-2 is genetically determined, and the aim of the present study was to evaluate the effect of MASP-2 levels on postoperative infection, recurrence and survival.

Experimental Design: MASP-2 concentrations were determined in serum from 605 patients collected before elective resection for primary colorectal cancer. The primary end points were postoperative infection, time to any recurrence, and time to death. The median time of follow-up was 7.9 years.

Results: MASP-2 levels were not correlated to postoperative infections (P = 0.49). High MASP-2 levels significantly correlated with recurrent cancer disease [P = 0.03; hazard ratio (HR) = 1.4; 95% confidence interval (CI), 1.0-2.0] and with poor survival (P = 0.0005; HR = 1.4; 95% CI, 1.2-1.7). Multivariate statistical analysis, including age, gender, Dukes' stage of disease, tumor localization, and postoperative pneumonia, showed that the MASP-2 level had an independent prognostic value in the patients (P = 0.0001; HR = 1.5; 95% CI, 1.2-1.8).

Conclusion: In the cohort of patients with colorectal cancer investigated, MASP-2 concentration in serum proved to be an independent prognostic marker with high MASP-2 levels predicting recurrence and poor survival. Postoperative infection could not be shown to be associated with MASP-2 levels.

Key Words: infectious complications • MBL • complement • survival • prognosis