Plasma YKL-40 as a biomarker in patients with nonmetastatic bone and soft tissue sarcomas: a prospective exploratory clinical study

Abstract

Purpose: YKL-40 is a glycoprotein with a role in inflammation, tissue remodeling, tumor angiogenesis, and protection against apoptosis. We hypothesized that high preoperative plasma YKL-40 in patients with nonmetastatic bone and soft tissue sarcoma (STS) is associated with short overall survival (OS), and that plasma YKL-40 is an independent predictor for OS. Materials and methods: Plasma was collected preoperatively from 65 patients with nonmetastatic bone (n=14) or STS (n=51) in the lower extremities (n=43), the upper extremities (n=16) or the trunk wall/spine (n=6). All patients underwent surgical cancer treatment. Twenty patients developed metastases during the follow-up period (minimum 5 y). The plasma concentration of YKL-40 was determined by enzyme-linked immunosorbent assay. Results: Twenty-seven patients died [mean: 3.2 (range: 0.2–7.3) y postoperatively] and 38 patients were still alive after a follow-up of mean 6.9 (5.8–8.2) years postoperatively. Plasma YKL-40 was higher in patients who died during follow-up (P=0.008), in males (P=0.007) and in patients 61 years of age and above (P=0.001). The 5-year OS was 68% and OS was lower in patients with high (≥95% percentile age-corrected) plasma YKL-40 (P=0.021), age 61 years and above (P=0.013), high histologic malignancy grade (P=0.047) and male sex (P=0.051). Multivariable analysis showed that only plasma YKL-40 (age-corrected (hazard ratio=2.80, 95% confidence interval: 1.13–6.91, P=0.026) and malignancy grade (hazard ratio=9.9×107, 95% confidence interval: 0–∞, P=0.007) remained independent prognostic factors for OS. Conclusions: High preoperative plasma YKL-40 was related to short OS in patients with nonmetastatic bone and STS and plasma YKL-40 (age-corrected) was an independent prognostic risk factor for OS.