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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2021; 27(33): 5474-5487
Published online Sep 7, 2021. doi: 10.3748/wjg.v27.i33.5474
Neutrophil extracellular traps in gastrointestinal cancer
Zi-Qiang Chu, Ke-Cheng Zhang, Lin Chen
Zi-Qiang Chu, Graduate School, Chinese PLA General Hospital, Beijing 100853, China
Zi-Qiang Chu, Institute of Basic Medical Sciences, Chinese PLA General Hospital, Beijing 100853, China
Ke-Cheng Zhang, Lin Chen, Department of General Surgery, Chinese PLA General Hospital First Medical Center, Beijing 100853, China
Author contributions: Chu ZQ and Zhang KC contributed equally to this work; Chu ZQ designed and conceived the review; Chu ZQ and Zhang KC analysed the articles and wrote the manuscript; all authors have read and approved the final version.
Supported by Natural Science Foundation of Beijing for Youth, No. 7214252; and Program of Military Medicine for Youth, No. QNF19055.
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lin Chen, MA, MD, Chief Doctor, Professor, Department of General Surgery, Chinese PLA General Hospital First Medical Center, No. 28 Fuxing Road, Beijing 100853, China. chenlin@301hospital.com.cn
Received: January 26, 2021
Peer-review started: January 26, 2021
First decision: April 5, 2021
Revised: April 6, 2021
Accepted: August 11, 2021
Article in press: August 11, 2021
Published online: September 7, 2021
Processing time: 220 Days and 2.8 Hours
Abstract

Gastrointestinal (GI) cancer is a high-risk malignancy and is characterized by high mortality and morbidity worldwide. Neutrophil extracellular traps (NETs), a weblike structure consisting of chromatin DNA with interspersed cytoplasmic and granule proteins, are extruded by activated neutrophils to entrap and kill bacteria and fungi. However, accumulating evidence shows that NETs are related to the progression and metastasis of cancer. In clinical studies, NETs infiltrate primary GI cancer tissues and are even more abundant in metastatic lesions. The quantity of NETs in peripheral blood is revealed to be associated with ascending clinical tumour stages, indicating the role of NETs as a prognostic markers in GI cancer. Moreover, several inhibitors of NETs or NET-related proteins have been discovered and used to exert anti-tumour effects in vitro or in vivo, suggesting that NETs can be regarded as targets in the treatment of GI cancer. In this review, we will focus on the role of NETs in gastric cancer and colorectal cancer, generalizing their effects on tumour-related thrombosis, invasion and metastasis. Recent reports are also listed to show the latest evidences of how NETs affect GI cancer. Additionally, notwithstanding the scarcity of systematic studies elucidating the underlying mechanisms of the interaction between NETs and cancer cells, we highlight the potential importance of NETs as biomarkers and anti-tumour therapeutic targets.

Keywords: Neutrophil extracellular traps; Gastric cancer; Colorectal cancer; Biomarkers; Therapeutic targets

Core Tip: Neutrophil extracellular traps (NETs) have been reported to participate in progression and metastasis in gastrointestinal (GI) cancer. Recent reports demonstrate that NET formation is enhanced in GI cancer patients as well as some mouse models and that elevated levels of NETs indicate an adverse outcome in patients. Furthermore, NETs can trap disseminated cancer cells and assist the formation of metastatic lesions although the underlying mechanisms remain vague. More studies are needed before NETs can be used as reliable biomarkers and therapeutic targets in GI cancer.