Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2021; 27(25): 3888-3900
Published online Jul 7, 2021. doi: 10.3748/wjg.v27.i25.3888
Diverse expression patterns of mucin 2 in colorectal cancer indicates its mechanism related to the intestinal mucosal barrier
Guo-Lian Gan, Hua-Tao Wu, Wen-Jia Chen, Chun-Lan Li, Qian-Qian Ye, Yi-Feng Zheng, Jing Liu
Guo-Lian Gan, Hua-Tao Wu, Yi-Feng Zheng, Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
Wen-Jia Chen, Chun-Lan Li, Qian-Qian Ye, Jing Liu, Changjiang Scholar’s Laboratory, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Wen-Jia Chen, Chun-Lan Li, Qian-Qian Ye, Jing Liu, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Wen-Jia Chen, Chun-Lan Li, Qian-Qian Ye, Jing Liu, Department of Physiology, Shantou University Medical College, Shantou 515041, Guangdong Province, China
Author contributions: Liu J and Zheng YF contributed to the conception and design of the study; Gan GL and Wu HT performed most of the experiments, analyzed the data, and drafted and revised the manuscript carefully; Chen WJ, Li CL, Ye QQ, and Zheng YF performed some of the experiments and interpreted the data; Wu HT, Zheng YF, and Liu J provided essential reagents; Liu J assisted with the experimental design and data analysis, and revised the original manuscript critically; all authors contributed to manuscript revision, and read and approved the submitted version.
Supported by National Natural Science Foundation of China, No. 81501539; the Natural Science Foundation of Guangdong Province, China, No. 2016A030312008; Science and Technology Planning Project of Shantou, China, No. 200617105260368; Medical Scientific Research Foundation of Guangdong, China, No. A2020627; and “Dengfeng Project” for the Construction of High-level Hospital in Guangdong Province—The First Affiliated Hospital of Shantou University College Supporting Funding, No. 202003-10.
Institutional review board statement: The current study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Shantou University Medical College.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: No conflict of interest is claimed by any author.
Data sharing statement: No additional data are available.
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: Jing Liu, MD, PhD, Associate Professor, Changjiang Scholar’s Laboratory, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong Province, China. jliu12@stu.edu.cn
Received: January 29, 2021
Peer-review started: January 29, 2021
First decision: February 25, 2021
Revised: March 11, 2021
Accepted: June 4, 2021
Article in press: June 4, 2021
Published online: July 7, 2021
ARTICLE HIGHLIGHTS
Research background

At present, several studies have reported abnormal expression patterns of mucin 2 (MUC2) in cancerous lesions, including colorectal cancer (CRC). However, as a member of the intestinal mucosal mechanical barrier, the relationship between MUC2 and the intestinal mucosal barrier in patients with CRC remains unclear. Revealing this association will help us more fully understand the role of MUC2 in CRC.

Research motivation

Although many studies have proved that intestinal mucosal barrier function is impaired and MUC2 expression is abnormal in patients with CRC, the direct relationship between MUC2 and intestinal mucosal barrier has rarely been studied. The main problem to be solved in this study is to clarify this relationship and lay a foundation for further studies on the molecular mechanism of MUC2 involvement in CRC.

Research objectives

This study aimed to explore abnormal expression patterns of MUC2 and the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC. The findings will provide a basis for further study of the pathogenesis of MUC2 in the process of intestinal mucosal barrier damage in CRC.

Research methods

Immunohistochemical staining was performed on cancer tissue and normal tissue samples from 100 patients with CRC to evaluate the expression of MUC2 in two different tissues, and these patients were followed for 12-60 mo to understand the overall survival (OS) and disease-free survival (DFS). Preoperative serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC) in 66 patients with CRC were detected by enzyme-linked immunosorbent assay and compared with those in 20 normal controls, so as to evaluate the damage of intestinal mucosal barrier in patients with CRC. The statistical methods involved in this study include χ2 test, Fisher’s exact test, Kaplan-Meier curve, and log-rank tests.

Research results

Immunohistochemical staining results showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and the expression of MUC2 was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05), but not significantly related to the patient’s age, sex, tumor location, size, depth of invasion, or degree of differentiation. The serum levels of MUC2, DAO, and D-LAC in patients with CRC were higher than those in normal people (P < 0.05), and were positively associated with serum levels of human DAO (χ2 = 3.957, P < 0.05) and D-LAC (χ2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barriers. It was suggested that the intestinal mucosal barrier was damaged, and MUC2 can also be used as a new evaluation index. The serum levels of MUC2 were correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). It seems to be a trend that patients with higher malignancy and later stage of tumors have higher serum MUC2 levels. Survival analysis showed that decreased expression of MUC2 in CRC tissues predicted a poor survival. The expression of MUC2 in tissues was significantly correlated with DFS (P = 0.032) and OS (P = 0.037). And the recurrence rate of patients with low expression of MUC2 was higher than that of patients with high expression of MUC2 (40% vs 18.5%, χ2 = 5.485, P < 0.05).

Research conclusions

MUC2 in the intestinal tissue may play a protective role on the intestine, which can be used as an indicator to evaluate the prognosis of CRC patients. Intestinal mucosal barrier function of CRC patients is impaired, and the serum MUC2 level can reflect the severity of the damage.

Research perspectives

Future researchers can further study the molecular mechanism of MUC2 in the process of intestinal mucosal barrier damage, which may reveal the pathological mechanism of CRC from a new perspective and provide a basis for the development of new targeted therapy drugs. In addition, related research can also be carried out in inflammatory bowel disease.