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
Abstract
BACKGROUND

Tubular adenocarcinoma of the colon, which originates from the epithelium of the 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 to the diagnosis and treatment of tubular adenocarcinoma. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted protein that 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 development. They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon.

AIM

To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon.

METHODS

Samples were collected from surgically excised tissue from various patients. The content of pro-gastrin-releasing peptide (pro-GRP) in the serum was measured by an electrochemiluminescence immunoassay. The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR, Western blotting and immunohistochemical analysis.

RESULTS

In this study, we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy. By analyzing the expression of NGAL in tubular adenocarcinoma at different levels, we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues. The upregulation of NGAL expression 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. When using NGAL as a biomarker for diagnosis, the accuracy was similar to that achieved with the widely used biomarker pro-GRP, suggesting that NGAL is reliable. Moreover, the expression of MMP-9 was also strongly correlated with the differentiation stage, demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon. More importantly, the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma, and these results were further confirmed by immunohistochemical analysis of tissue sections.

CONCLUSION

Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.

Keywords: Tubular adenocarcinoma; Colon; Neutrophil gelatinase-associated lipocalin; Matrix metalloproteinase-9; Biomarker

Core Tip: Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted protein, which modulates the expression of matrix metalloproteinase-9 (MMP-9) and is present in various cancers. However, it has not been determined whether NGAL or MMP-9 can be used as biomarkers in the diagnosis of tubular adenocarcinoma of the colon. In the present study, we demonstrated that both NGAL and MMP-9 could be used as biomarkers for diagnosis of tubular adenocarcinoma of the colon. By using them together, diagnositic accuracy can be further improved.