A high serum level of YKL-40 in patients with cervical cancer is associated with short survival

Abstract

21004 Background: YKL-40 is secreted by tumor cells, macrophages and neutrophils. The exact function of YKL-40 in cancer is unknown. It may be a growth, differentiation or survival factor and play a role in angiogenesis. High serum levels of YKL-40 are associated with a poor prognosis in a variety of solid and hematological malignancies. The aim of this study was to examine if serum YKL-40 is a prognostic biomarker in patients with cervical cancer. Methods: YKL-40 was determined by ELISA (Quidel, Santa Clara, CA) in pretreatment serum samples from 116 patients with cervical cancer (FIGO stage Ia (N=5), Ib (N=55), II (N=27), III (N=25) and IV (N=4); median age 50, range 27–87 years). The median follow-up time was 3.2 years (range 2.1–4.4 years). 18 patients had a recurrence and 28 patients died. Results: Serum YKL-40 was increased (p<0.001) in the patients with cervical cancer (median 76 μg/l, range 20–2310) compared to healthy women (43 μg/l, range 20–172). Serum YKL-40 was higher than the age-corrected 95th percentile of serum YKL-40 in healthy women in 35% of the patients. Patients with high serum YKL-40 had significantly shorter survival than patients with normal serum YKL- 40 (HR=3.1, 95% CI: 1.5–6.5, p=0.002, logrank test). Univariate Cox analysis of serum YKL-40 (log transformed and treated as a continuous covariate) showed significant association with overall survival (HR=2.3, 95% CI: 1.7–3.2, p<0.0001). Multivariate Cox analysis including stage, menopausal status and serum YKL-40 (log transformed and treated as a continuous covariate) showed that stage (stage II+III vs. I: HR=6.4, 95% CI: 1.8–22.5, p=0.004) and serum YKL-40 (HR=1.6, 95% CI: 1.1–2.4, p=0.02) were independent prognostic variables of overall survival. Univariate Cox analysis of serum YKL-40 (log transformed and treated as a continuous covariate) demonstrated a significant association with risk of recurrence (HR=1.7, 95% CI: 1.1–2.7, p=0.02). Conclusion: Serum YKL-40 is a prognostic biomarker of recurrence-free and overall survival in patients with cervical cancer. No significant financial relationships to disclose.