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
Research background

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and lethal human malignancies. With improvements in the diagnosis, staging system and treatment strategies, the overall 5-year survival rate of ESCC patients yielded a slight increase. However, patients at the same stage undergoing similar treatment regimens often have quite different clinical outcomes, which suggests that the current staging system is inadequate for predicting survival. Therefore, the identification of accurate biomarkers for ESCC is necessary to improve the clinical outcome of patients.

Research motivation

Elevated serum chitinase 3-like 1 (CHI3L1) is notably correlated with a poor prognosis and short survival in many malignant tumors. However, no observation concerning the role of CHI3L1 in ESCC prognosis has been reported. In addition, previous studies suggest that CHI3L1 in human tumors are expressed either by cancer cells or stromal cells, such as macrophages. However, no observations concerning the cell specific expression in ESCC were published previously.

Research objectives

To identify whether CHI3L1 serves as a suitable biomarker for the prognosis of ESCC and to analyze this protein’s cellular source.

Research methods

ELISA was conducted to detect the concentration of CHI3L1 in serum of 150 ESCC patients. Immunohistochemistry (IHC) was reanalyzed and fluorescent staining utilized to explore the cellular origins of CHI3L1. Cytokines in serum samples were measured with BD CBA Th1/Th2/Th17 Cytokine Kit. We stimulated the monocyte-derived macrophages (MDMs) with either interleukin-6 (IL-6) or the supernatant of ESCC cell line Eca-109 and then investigated the level of CHI3L1 by qPCR and ELISA.

Research results

This study finds that the level of serum CHI3L1 in patients with ESCC provides a reference mark for evaluating prognosis. In addition, the ESCC microenvironment, in our study, especially the secretion of IL-6 by esophageal tumor cells promotes the macrophage production of CHI3L1.

Research conclusions

This study first established a connection between pretreated CHI3L1 and patients with ESCC, and the serum CHI3L1 was primarily secreted by ESCC surrounded macrophages, suggesting that CHI3L1 was a simple, non-invasive and inexpensive prognostic factor. These finding may help to identify high-risk patients for treatment decisions and to understand the mechanisms of ESCC.

Research perspectives

Further studies are needed to determine how CHI3L1, produced by ESCC-associated macrophages, influences the development of ESCC. As CHI3L1 is reported to be associated with the malignant behavior, especially angiogenesis. We will seek whether it plays a role on the development of ESCC through promoting angiogenesis. And which type of macrophage, M1 or M2, is responsible for the secretion of CHI3L1 remains to be further explored.