Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1506
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
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.
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.
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.
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.
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.
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.
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.