title: 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.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark. anne.roslind@dadlnet.dk
authors.forename: Anne
authors.initials: A
authors.lastname: Roslind
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.forename: Eva
authors.initials: E
authors.lastname: Balslev
authors.forename: Dorte L
authors.initials: DL
authors.lastname: Nielsen
authors.forename: Jens
authors.initials: J
authors.lastname: Bentzen
authors.forename: Paul A
authors.initials: PA
authors.lastname: Price
authors.forename: Elo
authors.initials: E
authors.lastname: Andersen
mesh_terms: D054392:Adipokines; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000401:mortality / Q000628:therapy; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000401:mortality / Q000628:therapy; D006801:Humans; D037102:Lectins; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D054392:Adipokines; D001324:Autoantigens; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins