High serum YKL-40 level in patients with extended small cell lung cancer is related to short survival

Abstract

7219 Background: YKL-40 is secreted by cancer cells, macrophages and neutrophils. YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. Its function in cancer diseases is unknown. High serum YKL-40 levels in patients with colorectal-, metastatic breast- and ovarian carcinoma are associated with a poorer prognosis compared to patients with normal serum YKL-40. The aim was to evaluate the association of serum YKL-40 in small cell lung cancer (SCLC) patients and disease severity. Methods: YKL-40 was determined by RIA in serum from 131 SCLC patients (82 males and 49 females; aged 37–79 years, median 57 years) prior to chemotherapy with combinations of platin analogues, podophyllotoxin derivatives, alkylating agents and vinca alkaloids. The patients were followed until death or at least 64 months. The median survival time was 7.7 months. 127 patients died from SCLC during the study. Serum YKL-40 was also determined in 260 controls (aged 18–79 years, median 48 years). Results: Serum YKL-40 was elevated in patients with limited disease (LD) (N=59, median 149 μg/l, range 48–870, p=0.019) and in patients with extensive disease ( ED) (N=72, 210 μg/l, 56–2481, p<0.001) compared to controls. 22% of the patients with LD and 40% with ED had elevated serum YKL-40. The median survival was 5.1 months for patients with elevated serum YKL-40 and 9.0 months for patients with normal serum YKL-40. Patients with ED and elevated serum YKL-40 had an increased hazard for death within the first 6 months after start of chemotherapy compared to patients with normal serum YKL-40 (HR=2.31, 95% CI: 1.27–4.21, p=0.006). This was not found for patients with LD. Multivariate Cox analysis including sex, age, disease extension, performance status, serum LDH and YKL-40 showed that serum YKL-40 in patients with ED (HR=2.41, 95% CI: 1.07–5.46, p=0.03) and age (HR=1.87, 95% CI: 1.16–3.02, p=0.01) were independent prognostic variables of survival within the first 6 months. Conclusions: These results suggest that elevated serum YKL-40 in patients with SCLC is related to disease extension and early death. Studies are needed to determine the function of YKL-40 in SCLC. No significant financial relationships to disclose.