State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China.
Department of Biotechnology, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China.
World J Gastroenterol. 2017 Nov 21;23(43):7693-7704. doi: 10.3748/wjg.v23.i43.7693.
To identify whether chitinase 3-like 1 (CHI3L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma (ESCC) and to analyze this protein's cellular source.
An ELISA was conducted to detect the concentration of CHI3L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed, and fluorescent staining was utilized to explore the cellular origins of CHI3L1. We stimulated monocyte-derived macrophages (MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3L1 by qPCR and ELISA.
The level of serum CHI3L1 was higher in older patients (≥ 60) than in patients under the age of 60 ( = 0.001). The patients with higher levels of CHI3L1 had a significantly shorter overall survival, whereas the traditional markers, carcinoembryonic antigen and squamous cell carcinoma antigen, were less effective ( > 0.05). A multivariate Cox analysis ( = 0.001) indicated that CHI3L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3L1. Interleukin-6 (IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3L1. The serum concentration of CHI3L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil (NEU, = 0.045), neutrophil/lymphocyte rate (NLR, = 0.016), and C-reactive protein (CRP, < 0.001).
Our study first established a connection between the pretreated CHI3L1 and patients with ESCC, and the serum CHI3L1 was primarily secreted by ESCC-surrounded macrophages.
确定几丁质酶 3 样蛋白 1（CHI3L1）是否可作为预测食管鳞状细胞癌（ESCC）预后的合适生物标志物，并分析该蛋白的细胞来源。
采用 ELISA 法检测 2001 年 1 月至 2005 年 2 月期间诊断的 150 例 ESCC 患者血清中 CHI3L1 的浓度。采用 Kaplan-Meier 和 Cox 回归分析评估 CHI3L1 的预后相关性。重新分析免疫组织化学结果，并采用荧光染色法探讨 CHI3L1 的细胞来源。我们用白细胞介素 6（IL-6）或 ESCC 细胞系 Eca-109 的上清液刺激单核细胞衍生的巨噬细胞（MDMs），然后通过 qPCR 和 ELISA 检测 CHI3L1 的水平。
血清 CHI3L1 水平在年龄较大（≥60 岁）的患者中高于年龄较小的患者（=0.001）。CHI3L1 水平较高的患者总生存期明显缩短，而传统标志物癌胚抗原和鳞状细胞癌抗原则效果较差（>0.05）。多变量 Cox 分析（=0.001）表明，CHI3L1 是 ESCC 患者的独立预后因素。ESCC 肿瘤周围的巨噬细胞表达高水平的 CHI3L1。白细胞介素 6（IL-6）和含有 IL-6 的 Eca-109 上清液刺激 MDMs 分泌 CHI3L1。ESCC 患者血清 CHI3L1 浓度与实验室炎症参数中性粒细胞（NEU，=0.045）、中性粒细胞/淋巴细胞比值（NLR，=0.016）和 C 反应蛋白（CRP，<0.001）呈弱相关。
本研究首次建立了预处理 CHI3L1 与 ESCC 患者之间的联系，并且血清 CHI3L1 主要由 ESCC 周围的巨噬细胞分泌。
