Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1506-1517
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1506
Combination of neutrophil gelatinase-associated lipocalin and matrix metalloproteinase-9 are biomarkers for the detection of colon tubular adenocarcinoma
Jun-Hua Yuan, Li-Shuang Xie, Yu-Hua Zhu, Xiao-Hua Wang, Yi-Jing Zhang, Xiao-Jun Wang
Jun-Hua Yuan, Yi-Jing Zhang, Xiao-Jun Wang, Department of Geriatric Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Li-Shuang Xie, Medical Records Room, Yinan County People’s Hospital, Yinan 276399, Shandong Province, China
Yu-Hua Zhu, Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Xiao-Hua Wang, Department of Infectious Diseases and Liver Diseases, Jinan Infectious Disease Hospital, Shandong University School of Medicine, Jinan 250021, Shandong Province, China
Author contributions: Yuan JH, Xie LS and Zhang YJ designed the research; Yuan JH, Wang XH and Zhu YH performed the experiments; Xie LS, Zhang YJ and Wang XJ analyzed the data and participated in the discussion; Yuan JH and Xie LS wrote and revised the paper; all authors reviewed the manuscript.
Supported by Shandong Key Research and Development Plan, No. 2016GSF201020.
Institutional review board statement: The study was reviewed and approved by the “Shenghua Hospital of Shandong Province, Biomedical Research Ethics Committee” Institutional Review Board (Approval No.2021-005).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Jun-Hua Yuan, MD, Chief Physician, Department of Geriatric Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Huaiyin District, Jinan 250021, Shandong Province, China. yjh717299@126.com
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: April 19, 2021
Revised: April 22, 2021
Accepted: July 21, 2021
Article in press: July 21, 2021
Published online: October 15, 2021
Processing time: 216 Days and 0.8 Hours
ARTICLE HIGHLIGHTS
Research background

Tubular adenocarcinoma of the colon, which originates from the epithelium of glands, is a major health concern worldwide. However, it is difficult to detect at an early stage. The lack of biomarkers is a main barrier in the diagnosis and treatment of tubular adenocarcinoma. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted protein, which induces the expression of matrix metalloproteinase-9 (MMP-9) and is involved in various tumors. NGAL and MMP-9 have been reported to be associated with tumorigenesis and tumor development. They may be potential biomarkers for the diagnosis of tubular adenocarcinoma of the colon.

Research motivation

The combination of NGAL and MMP9 are promising biomarkers for the early detection of tubular adenocarcinoma of the colon. To evaluate whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon, it may be beneficial to detect this tumor at the molecular level in the very early stage.

Research objectives

We evaluated whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon as patients with this disease will require early diagnosis and treatment.

Research methods

Samples were collected from the colonic mucosa of various patients. Ten patients had polyps (I), 10 patients had mild tubular adenocarcinoma (II) and 10 patients had severe tubular adenocarcinoma (III), respectively, confirmed by a pathologist. In addition, 10 normal samples were included as controls. The content of pro-gastrin-releasing peptide (pro-GRP) in serum was measured by an electrochemiluminescence immunoassay. The mRNA expression of NGAL and MMP-9 was examined by quantitative real-time PCR (qRT-PCR) analysis, and their protein expression was examined by Western blotting and immunohistochemical (IHC) analysis. According to the status of tubular adenocarcinoma of the colon, the patients were divided into three groups. Thus, the clinical grouping in this research was novel, which has not adopted in other studies.

Research results

In this study, we found that NGAL and MMP-9 can be used as biomarkers for detecting tubular adenocarcinoma of the colon and their combination resulted in better diagnostic accuracy. By analyzing the expression of NGAL in tubular adenocarcinoma at different levels, we found that NGAL was significantly up-regulated in primary tubular adenocarcinoma compared with normal tissues. The up-regulation of NGAL was strongly correlated with both the degree of differentiation and the disease stage (I–III), indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma. Using NGAL as a biomarker for diagnosis, the accuracy was similar to the widely used biomarker pro-GRP, suggesting that NGAL is a reliable biomarker. In addition, the expression of MMP-9 was also strongly correlated with differentiation and stage, demonstrating that MMP-9 can be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon. More importantly, the combination of NGAL and MMP-9 achieved greater diagnostic accuracy in tubular adenocarcinoma, and these results were further confirmed by immunohistochemical analysis of tissue sections.

Research conclusions

In this study, the up-regulation of NGAL and MMP-9 was strongly correlated with both the degree of differentiation and stage of tubular adenocarcinoma of the colon. Both NGAL and MMP-9 can be used as biomarkers for detecting tubular adenocarcinoma of the colon and their combination achieved better diagnostic accuracy. Patients who develop tubular adenocarcinoma of colon will require early diagnosis and early treatment.

Research perspectives

It is necessary to study more cases of tubular adenocarcinoma of the colon as other factors may be involved in the progression of this disease. A larger scale clinical study may be the best method for future research on this tumor.