High serum levels of YKL-40 in patients with squamous cell carcinoma of the head and neck are associated with short survival

Abstract

YKL-40 is a glycoprotein secreted by macrophages, neutrophils and malignant tumor cells. Elevated serum levels of YKL-40 are associated with poor prognosis in several malignancies. In this study, we examined the prognostic value of serum YKL-40 before treatment and during follow-up in patients with squamous cell carcinoma of the head and neck (HNSCC). YKL-40 was determined by ELISA retrospectively in serum from 173 patients with primary HNSCC before treatment and up to 2 years after treatment. Median follow-up time was 7.9 years. YKL-40 protein expression in tumor biopsies was assessed by immunohistochemistry in 50 patients. Pretreatment serum YKL-40 was elevated in 53%. Patients with high serum YKL-40 had shorter survival than patients with normal serum YKL-40 (33 vs. 84 months; p = 0.008). Multivariate Cox analysis including pretreatment serum YKL-40, age, sex, primary tumor site, TNM classification and treatment demonstrated that TNM classification (HR = 2.61, p = 0.02) and serum YKL-40 (log-transformed continuous variable: HR = 1.55, p < 0.0001) were independent prognostic variables of overall survival (OS). Multivariate Cox analysis demonstrated that TNM classification (HR = 5.77, p = 0.001) and serum YKL-40 (dichotomous variable: HR = 2.75, p = 0.01) were independent predictors of recurrence-free survival. During follow-up after radiotherapy, a high serum YKL-40 (log-transformed continuous variable) in patients with TNM Stage III and IV disease predicted poorer OS within 6 months (HR = 1.95, p < 0.0001). Immunohistochemical analysis showed YKL-40 expression in the malignant tumor cells. In conclusion, serum YKL-40 was demonstrated to be an independent prognostic biomarker of recurrence-free and overall survival in patients with HNSCC.