Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1808-1822
Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1808
Clinical implications of interleukins-31, 32, and 33 in gastric cancer
Qing-Hua Liu, Ji-Wei Zhang, Lei Xia, Steven G Wise, Brett David Hambly, Kun Tao, Shi-San Bao
Qing-Hua Liu, Lei Xia, Department of Pathology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
Ji-Wei Zhang, Department of Surgery, The Central Hospital of Songjiang District, Shanghai Jiaotong University, Shanghai 201699, Shanghai, China
Steven G Wise, Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Sydney 2006, NSW, Australia
Brett David Hambly, Kun Tao, Shi-San Bao, Department of Pathology,Tongren Hospital, Shanghai 200336, China
Author contributions: Liu QH collected the samples, performed the histopathological and immunohistochemical examinations, analysed the data, and wrote the paper; Zhang JW collected the samples, analysed the data, and wrote the paper; Liu QH and Zhang JW contributed equally to the study; Xia L performed ELISA and data analysis; Wise SG provided intellectual input; Hambly BD and Tao K revised the manuscript and provided intellectual input; Bao SS designed the experiment and revised the manuscript.
Supported by the National Natural Science Foundation of China, No. 81502030.
Institutional review board statement: This study was approved by the Human Ethics Committee, the Institutional Review Boards of Affiliated Hospital of Xuzhou Medical University and conducted in accordance with the Declaration of Helsinki.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors declare that no financial or other conflict of interest exists in relation to the content of the article.
Data sharing statement: The data can be available upon request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shi-San Bao, MD, PhD, Academic Fellow, Department of Pathology, Tongren Hospital, No. 1111 Xianxia Road, Changning District, Shanghai 200336, China. profbao@hotmail.com
Received: February 28, 2022
Peer-review started: February 28, 2022
First decision: April 17, 2022
Revised: April 21, 2022
Accepted: July 31, 2022
Article in press: July 31, 2022
Published online: September 15, 2022
Processing time: 192 Days and 13.4 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality. Despite the more widespread use of recent diagnostic techniques, including endoscopic examination, many GC patients are diagnosed at advanced stages, resulting in a poor 5-year survival rate, emphasizing the critical need for development of a reliable biomarker(s) with high specificity and sensitivity to improve the prediction of prognosis for more successful outcomes for GC patients. Endoscopic examination provides a useful approach in the early detection of GC, and in reducing cancer-related mortality.

Research motivation

The cell-mediated immune response is extremely important in defence against tumour development, since compromised host immunity is known to contribute to the establishment, proliferation, and metastasis of malignant tumours. Although high host inflammatory status has been reported in the tumour microenvironment, an incompetent inflammatory/immune response will lead to tumour progression.

Research objectives

We aimed to identify the expression of interleukin (IL)-31, IL-32, and IL-33 in GC and assess their inter-correlation and clinical significance.

Research methods

GC tissues were obtained from patients without local recurrences for immunohistochemistry to determine the expression of IL-31, IL-32, and IL-33. Additionally, circulating levels of IL-31, 32, 33 were determined using ELISA. The Mann-Whitney U test or the Kruskal-Wallis test was used for statistical analysis.

Research results

IL-31, IL-32, and IL-33 expression was all lower in GC than in adjacent non-cancer gastric tissues (P < 0.05). IL-33 level in peripheral blood of GC patients was significantly lower than that of healthy individuals (1.50 ± 1.11 vs 9.61 ± 8.00 ng/mL, (P < 0.05). Decreased IL-31, IL-32, and IL-33 expression in GC was observed in younger patients (< 60 years), and IL-32 and IL-33 expression was lower in female patients (P < 0.05). Higher IL-32 expression correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM stage I-II. Univariate/multivariate analysis revealed that IL-32 was an independent prognostic factor for GC in the T4 stage subgroup. Circulating IL-33 was significantly lower in GC patients at TNM stage IV than in healthy people (P < 0.05).

Research conclusions

IL-31, IL-32, and IL-33 expression in GC is all decreased, which correlates with younger age of the GC patients. IL-32 and IL-33 expression also correlates with the sex of the GC patients. Decreased IL-32 correlates with a poorer survival of GC patients in the T4 stage and TNM stage I-II subgroups. Down-regulation of IL-32 is an independent prognostic factor for survival of T4 GC patients. Finally, low IL-33 in peripheral blood may be considered as an objective predictive marker for the development of GC.

Research perspectives

Further studies are required to investigate the mechanism of action of these ILs in GC.