Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2022; 14(7): 1295-1306
Published online Jul 15, 2022. doi: 10.4251/wjgo.v14.i7.1295
Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients
Ying-Li Fu, Yan-Hua Wu, Dong-Hui Cao, Zhi-Fang Jia, Ao Shen, Jing Jiang, Xue-Yuan Cao
Ying-Li Fu, Yan-Hua Wu, Dong-Hui Cao, Zhi-Fang Jia, Jing Jiang, Division of Clinical Research, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
Ao Shen, Xue-Yuan Cao, Department of Gastric and Colorectal Surgery, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
Author contributions: Cao XY conceived and designed the study; Fu YL and Wu YH conducted data analysis and drafted the manuscript, and they contributed equally to this work; Cao DH, Jia ZF and Shen A collected data and biospecimens on gastric cancer patients; Jiang J measured the level of 5-hmC; All authors approved the final version for submission.
Supported by National Natural Science Foundation of China, No. 81874279; Scientific and Technological Development Program of Jilin Province, No. 20190201093JC and No. 20200201326JC; Jilin Province Department of Finance, No. JLSWSRCZX2020-010; and Youth Development Fund from First Hospital of Jilin University, No. JDYY11202021.
Institutional review board statement: This study was approved by the First Hospital of Jilin University Institutional Review Board (Approval No.2021-493).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declared no competing financial interests.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at email
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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:
Corresponding author: Xue-Yuan Cao, PhD, Professor, Research Scientist, Department of Gastric and Colorectal Surgery, The First Hospital of Jilin University, Xinmin Street, Changchun 130000, Jilin Province, China.
Received: January 11, 2022
Peer-review started: January 11, 2022
First decision: March 13, 2022
Revised: March 18, 2022
Accepted: May 28, 2022
Article in press: May 28, 2022
Published online: July 15, 2022
Research background

Most gastric cancer (GC) patients are diagnosed at middle or late stage because the symptoms in early stage are obscure, which causes higher mortality rates of GC. Analyses show that aberrant DNA methylation is highly correlated with GC risk. Helicobacter pylori (H. pylori) was identified as a class I carcinogen leading to gastric adenocarcinoma, and H. pylori-induced chronic inflammation plays a direct role in the induction of aberrant DNA methylation. The median demethylation product 5-hydroxymethylcytosine (5-hmC) is considered as an activating epigenetic marker, and it plays complex roles in gene regulation of tumorigenesis.

Research motivation

A few small studies analyzed the association between 5-hmC levels and GC, but the evidence is lacking, especially for H. pylori-induced GC.

Research objectives

Exploring the association between 5-hmC level and the progression and prognosis of GC patients with or without H. pylori infection.

Research methods

This was a retrospective cohort study to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H. pylori infection status.

Research results

A high level of 5-hmC was an independent significant favorable predictor of overall survival in the entire GC patient cohort (hazard ratio = 0.61, 95% confidence interval: 0.38-0.98, P = 0.040), the H. pylori-negative GC subgroup (hazard ratio = 0.30, 95% confidence interval: 0.13-0.68, P = 0.004) and GC patients with early TNM stage (hazard ratio = 0.32, 95% confidence interval: 0.13-0.77, P = 0.011).

Research conclusions

5-hmC level was a significant predictor of the prognosis of GC patients without H. pylori infection.

Research perspectives

A large-scale GC patient cohort to assess the association between the level of 5-hmC and the prognosis of GC patients, especially for different H. pylori infection status, should be conducted.