Prognostic and predictive value of YKL-40 in stage IIB-III melanoma

Abstract

This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.

Obesity and melanoma: could fat be fueling malignancy?

“…Chitinase‐3‐like protein 1, best known as YKL‐40, is a glycoprotein secreted by AT macrophages (Iwata et al., ) and is increased in the serum of obese individuals (Catalan et al., ). Interestingly, this molecule is a strong independent prognostic factor for poor survival in melanoma patients (Krogh et al., ; Schmidt et al., ). Moreover, YKL‐40 plays a key role in melanoma pulmonary metastasis by creating a tumor permissive environment, in part by decreasing NK cell accumulation (Ma et al., ).…”

YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal–Regulated Kinase Pathways

“…Concerning malignancies, YKL-40 expression and function have been investigated mostly in solid malignancies. Elevated YKL-40 levels in the circulation were found in a variety of solid tumors, which frequently correlates with disease severity or predicts poor outcome (Krogh et al, 2016;Kzhyshkowska et al, 2016;Schmidt et al, 2006). YKL-40 has been shown to activate cancer signaling pathways and promote proliferation, angiogenesis, or metastasis of glioblastoma and colon cancer (Francescone et al, 2011;Kawada et al, 2012;Ku et al, 2011;Shao et al, 2009).…”

Anorectal mucosal melanoma

“…Recent studies are investigating the YKL-40 mechanisms of action, as well as its utility in anti- YKL-40 therapies [ 71 ] such us Interleukin-2 and interferon α [ 72 , 73 ].…”