Väänänen Tuija, Kallio Jukka, Vuolteenaho Katriina, Ojala Alexandra, Luukkaala Tiina, Hämäläinen Mari, Tammela Teuvo, Kellokumpu-Lehtinen Pirkko-Liisa, Moilanen Eeva
a The Immunopharmacology Research Group, Faculty of Medicine and Life Sciences , University of Tampere and Tampere University Hospital , Tampere , Finland.
b Department of Urology , Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere , Tampere , Finland.
Scand J Urol. 2017 Oct;51(5):367-372. doi: 10.1080/21681805.2017.1327885. Epub 2017 Jun 23.
YKL-40 is an inflammation-associated glycoprotein supposed to have a role in cell survival and angiogenesis. Renal cell carcinoma (RCC) is characterized by varying prognosis and risk of relapse after a disease-free period of years. Prognostic markers are critically needed. This study investigated whether YKL-40 could be a useful biomarker in RCC patients.
Blood samples from 82 patients with RCC were collected at the time of diagnosis and 3, 5 and 9 months and 2 and 3 years after nephrectomy. YKL-40 levels were determined by enzyme-linked immunosorbent assay. Survival of patients and relapse of RCC were followed up to 15 years.
Circulating YKL-40 levels were increased in patients with metastatic RCC at the time of diagnosis (median 115.7 ng/ml, interquartile range 61.0-221.6 ng/ml). Among patients primarily diagnosed with non-metastatic RCC, baseline YKL-40 levels were significantly higher in patients who experienced a relapse during follow-up (103.7, 59.3-242.0 ng/ml) than in patients without relapse (50.6, 33.8-97.1 ng/ml). High baseline YKL-40 was highly associated with poor prognosis in RCC: in age-adjusted univariate analysis, YKL-40 over 120 ng/ml (highest tertile) predicted over five-fold mortality in 5 years, and in multivariate analysis high YKL-40 remained a statistically significant independent risk factor for 5 and 15 year survival.
Increased circulating YKL-40 levels were significantly associated with poor survival in patients with RCC. The results suggest YKL-40 as a useful novel biomarker in evaluating prognosis and relapse risk in RCC, being especially beneficial in patients primarily diagnosed with non-metastatic RCC.
YKL-40是一种与炎症相关的糖蛋白,被认为在细胞存活和血管生成中发挥作用。肾细胞癌(RCC)的特点是预后各异,且在数年无病期后有复发风险。迫切需要预后标志物。本研究调查了YKL-40是否可能是RCC患者有用的生物标志物。
收集82例RCC患者诊断时以及肾切除术后3、5和9个月及2和3年时的血样。采用酶联免疫吸附测定法测定YKL-40水平。对患者的生存情况和RCC复发情况进行长达15年的随访。
转移性RCC患者诊断时循环YKL-40水平升高(中位数115.7 ng/ml,四分位间距61.0 - 221.6 ng/ml)。在最初诊断为非转移性RCC的患者中,随访期间复发患者的基线YKL-40水平(103.7,59.3 - 242.0 ng/ml)显著高于未复发患者(50.6,33.8 - 97.1 ng/ml)。高基线YKL-40与RCC的不良预后高度相关:在年龄校正的单因素分析中,YKL-40超过120 ng/ml(最高三分位数)预测5年内死亡率超过五倍,在多因素分析中,高YKL-40仍然是5年和15年生存的统计学显著独立危险因素。
RCC患者循环YKL-40水平升高与不良生存显著相关。结果表明YKL-40是评估RCC预后和复发风险的一种有用的新型生物标志物,对最初诊断为非转移性RCC的患者尤其有益。