Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2019; 11(12): 1141-1150
Published online Dec 15, 2019. doi: 10.4251/wjgo.v11.i12.1141
Protein expression trends of DNMT1 in gastrointestinal diseases: From benign to precancerous lesions to cancer
Tian-Miao Ma, Li-Ping Sun, Nan-Nan Dong, Ming-Jun Sun, Yuan Yuan
Tian-Miao Ma, Ming-Jun Sun, Department of Gastroenterology, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Li-Ping Sun, Nan-Nan Dong, Yuan Yuan, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Yuan Y contributed to study design and manuscript revision; Ma TM contributed to data interpretation, performed the experiments, and drafted the manuscript; Sun LP contributed to experiment instruction, data interpretation, and statistical analysis; Dong NN contributed to sample preparation; and Sun MJ contributed to sample collection and experimental instruction.
Institutional review board statement: The study was approved by the ethics committee of the First Hospital of China Medical University (Shenyang, China).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at yuanyuan@cmu.edu.cn
Open-Access: This article is an open-access article which 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yuan Yuan, MD, PhD, Professor, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, No. 155, Nanjingbei Street, Heping District, Shenyang 110001, Liaoning Province, China. yuanyuan@cmu.edu.cn
Telephone: +86-24-83282153
Received: March 30, 2019
Peer-review started: April 3, 2019
First decision: July 31, 2019
Revised: September 4, 2019
Accepted: September 12, 2019
Article in press: September 13, 2019
Published online: December 15, 2019
Processing time: 255 Days and 17 Hours
Abstract
BACKGROUND

In recent years, the incidence of gastrointestinal (GI) cancer in China has increased annually. Early detection and appropriate therapy are considered to be the key to treat GI cancer. DNMT1 takes an active part in the advancement of GI cancer, which will change as the disease progresses. But its expression characteristics in the dynamic variations of GI carcinogenesis are still unclear.

AIM

To investigate the expression characteristics of DNMT1 in different GI diseases.

METHODS

We detected the expression of DNMT1 in 650 cases of different GI diseases by immunohistochemistry, including 90 cases of chronic superficial gastritis (CSG), 72 cases of atrophic gastritis with intestinal metaplasia (AG/GIM), 54 cases of low-grade intraepithelial neoplasia (GLIN), 66 cases of high-grade intraepithelial neoplasia (GHIN), 71 cases of early gastric cancer (EGC), 90 cases of normal intestinal mucosa (NIM), 54 cases of intestinal low-grade intraepithelial neoplasia (ILIN), 71 cases of intestinal high-grade intraepithelial neoplasia (IHIN), and 82 cases of early colorectal cancer (ECRC).

RESULTS

In the CSG group, all cases showed weakly positive or negative expression of DNMT1. However, in other four groups (AG/GIM, GLIN, GHIN, and EGC), the positive expression rate gradually increased with the severity of the diseases; the negative or weakly positive cases accounted for 55.56% (40/72), 38.89% (21/54), 1.52% (1/66), and 1.41% (1/71), respectively. Besides, the moderately positive cases were 44.44% (32/72), 57.41% (31/54), 80.30% (53/66), and 43.66% (31/71), respectively. The strongly positive cases only existed in the GLIN (3.70%, 2/54), GHIN (18.18%, 12/66), and EGC (54.93%, 39/71) groups. The differences between any two groups were statistically significant (P < 0.05). Similarly, in the NIM group, cases with weakly positive expression of DNMT1 were predominant (91.11%, 82/90), and the rest were moderately positive cases (8.89%, 8/90). In the ILIN, IHIN, and ECRC groups, the rates of cases with weak or negative expression of DNMT1 were 46.30% (25/54), 12.68% (9/71), and 4.88% (4/82), respectively; with moderately positive expression were 53.70% (29/54), 71.83% (51/71), and 34.15% (28/82), respectively; and with strongly positive expression were 0.00% (0/54), 15.49% (11/71), and 60.98% (50/82), respectively. The differences between any two groups were also statistically significant (P < 0.05).

CONCLUSION

The overexpression of DNMT1 protein could effectively predict early GI cancers and severe precancerous lesions, which may have potential clinical application value.

Keywords: Gastric cancer; Colorectal cancer; DNMT1; Precancerous lesion; Intraepithelial neoplasia

Core tip: The expression of DNMT1 was significantly effective for screening precancerous lesions and cancers. DNMT1 could be a potential marker for the diagnosis of gastric cancer and colorectal cancer. At the same time, the fluctuation of its expression may suggest the progression of gastrointestinal diseases, which could be instructive for further examination and treatment.