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
Abstract
BACKGROUND

Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality.

AIM

To determine whether interleukin (IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients.

METHODS

Tissue array (n = 180) gastric specimens were utilised. IL-31, IL-32, and IL-33 expression in GC and non-GC tissues was detected immunohistochemically. The correlations between IL-31, IL-32, and IL-33 expression in GC and severity of clinicopathological parameters were evaluated. Survival curves were plotted using the Kaplan-Meier method/Cox regression. Circulating IL-31, IL-32, and IL-33 were detected by ELISA.

RESULTS

We found that the expression levels of IL-31, IL-32, and IL-33 were all lower in GC than in adjacent non-GC gastric tissues (P < 0.05). IL-33 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 in GC were observed in younger patients (< 60 years), and IL-32 and IL-33 were lower in female patients (P < 0.05). Higher IL-32 correlated with a longer survival in two GC subgroups: T4 invasion depth and TNM I-II stage. 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).

CONCLUSION

Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC and demonstrate their relative usefulness as prognostic markers for GC. The underlying mechanism of IL-31, IL-32, and IL-33 actions in GC should be further explored.

Keywords: Diagnosis and therapy; Gastric cancer; Immune cell interactions; Interleukin-31; Interleukin32; Interleukin-33

Core Tip: Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality. This study aimed to determine whether interleukin (IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients. IL-31, IL-32, and IL-33 expression in GC was correlated with the severity of clinicopathological parameters. Circulating IL-33 was significantly low in GC patients. Our findings may provide new insights into the roles of IL-31, IL-32, and IL-33 in the carcinogenesis of GC.