High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival.

Abstract

YKL-40 is a member of family 18 glycosyl hydrolases. YKL-40 is a growth factor and may stimulate migration of endothelial cells. YKL-40 may also play a role in inflammation and degradation of connective tissue. Elevated preoperative serum YKL-40 levels in patients with colorectal carcinoma are associated with a significantly poorer prognosis compared to patients with normal serum YKL-40. In the current study the authors evaluated the value of serum YKL-40 in monitoring patients with colorectal carcinoma. YKL-40 was determined by an in-house radioimmunoassay method in serum obtained pre- and postoperatively from 324 patients who underwent curative resection (Dukes Stage A: 47; B: 148; C: 119; and D: 10). The patients were followed with serum YKL-40 levels every 6 months postoperatively, and the median followup time was 82 months (range, 68-95). In that period 146 patients died. Serum YKL-40 was significantly decreased in the first postoperative blood sample in 62% of patients with high preoperative levels. In addition, patients with high serum YKL-40 (adjusted for age) six months after curative operation had significantly shorter survival times (P = 0.0002) and shorter relapse free intervals (P = 0.004) than patients with normal postoperative serum YKL-40. This result was independent of simultaneous serum carcinoembryonic antigen levels at six months. Analysis of survival by scoring serum YKL-40 as a time-dependent covariate in a Cox regression analysis showed that patients exhibiting elevated serum YKL-40 had an increased hazard for death within the following six months compared to those patients with normal serum YKL-40 level (hazard ratio [HR] = 9.6, 95% confidence interval [CI]: 6.0-15.5, P < 0.0001). Multivariate analysis including Dukes stage, age, gender, and tumor location as well as the time-dependent serum YKL-40 showed that high serum YKL-40 was an independent prognostic variable of survival (HR = 8.5, 95% CI: 5.3-13.7, P < 0.0001). These results suggest that determination of serum YKL-40 during followup of patients operated on for colorectal carcinoma might be useful for monitoring curatively resected patients.