Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2017; 23(43): 7693-7704
Published online Nov 21, 2017. doi: 10.3748/wjg.v23.i43.7693
Chitinase 3-like 1 secreted by peritumoral macrophages in esophageal squamous cell carcinoma is a favorable prognostic factor for survival
Shan Xing, Xin Zheng, Tao Zeng, Mu-Sheng Zeng, Qian Zhong, Yue-Song Cao, Kai-Lu Pan, Chu Wei, Fan Hou, Wan-Li Liu
Shan Xing, Xin Zheng, Tao Zeng, Mu-Sheng Zeng, Qian Zhong, Fan Hou, Wan-Li Liu, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China
Shan Xing, Xin Zheng, Tao Zeng, Fan Hou, Wan-Li Liu, Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Yue-Song Cao, Department of Biotechnology, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
Kai-Lu Pan, Chu Wei, Department of Clinical Laboratory, Guangdong Medical University, Dongguan 523808, Guangdong Province, China
Author contributions: Xing S and Zheng X contributed equally to this work; Xing S, Zheng X and Liu WL participated in the experimental design and carried out the experiments; Xing S and Liu WL drafted the manuscript and interpreted the data; Cao YS, Pan KL and Wei C collected the samples; Zeng T and Hou F took part in the acquisition of the data; Zeng MS and Zhong Q provided experimental guidance; and all the authors read and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Sun Yat-sen University Cancer Center.
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Wan-Li Liu, PhD, Professor, Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, Guangdong Province, China.
Telephone: +86-20-87343196 Fax: +86-20-87343196
Received: June 30, 2017
Peer-review started: June 30, 2017
First decision: August 15, 2017
Revised: September 13, 2017
Accepted: September 26, 2017
Article in press: September 26, 2017
Published online: November 21, 2017

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 (P = 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 (P > 0.05). A multivariate Cox analysis (P = 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, P = 0.045), neutrophil/lymphocyte rate (NLR, P = 0.016), and C-reactive protein (CRP, P < 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.

Keywords: Esophageal squamous cell carcinoma, Prognostic biomarker, Chitinase 3-like 1, Macrophage, Esophageal squamous cell carcinoma

Core tip: The current staging system is inadequate for predicting post-treated survival. Our study first established a connection between pretreated chitinase 3-like 1 (CHI3L1) and patients with esophageal squamous cell carcinoma (ESCC), and serum CHI3L1 was primarily secreted by ESCC-surrounded macrophages, suggesting that CHI3L1 was a simple and inexpensive prognostic factor. This simple, convenient serological testing allows for clinical application. In addition, in our study, the ESCC microenvironment, especially the secretion of IL - 6 by esophageal tumor cells, promotes the macrophage production of CHI3L1. These findings might help to identify high-risk patients for treatment decisions and to elucidate the mechanisms of ESCC.