Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Mar 27, 2023; 15(3): 346-361
Published online Mar 27, 2023. doi: 10.4240/wjgs.v15.i3.346
Differential expression and significance of 5-hydroxymethylcytosine modification in hepatitis B virus carriers and patients with liver cirrhosis and liver cancer
Yue-Cui Li, Wei-Yue Hu, Cheng-Hang Li, Li-Li Zhang, Xiang-Wei Xu, Jin Li, Hong-Xia Luo
Yue-Cui Li, Wei-Yue Hu, Cheng-Hang Li, Li-Li Zhang, Xiang-Wei Xu, Jin Li, Hong-Xia Luo, Department of Infectious Diseases, The First People’s Hospital of Yongkang, Jinhua 321300, Zhejiang Province, China
Author contributions: Li YC and Hu WY conceived the experimental ideas; Hu WY and Li CH performed the data collection; Zhang LL, Xu XW, Li J and Luo HX completed data sorting and analysis; Li YC wrote this manuscript.
Supported by Science and Technology Planning Project of Zhejiang Province, No. LGF20H160001.
Institutional review board statement: The study was reviewed and approved by The First People’s Hospital of Yongkang Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this study.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yue-Cui Li, MBChB, Chief Physician, Department of Infectious Diseases, The First People’s Hospital of Yongkang, No. 599 Jinshan West Road, Yongkang, Jinhua 321300, Zhejiang Province, China. liyuecui02@yeah.net
Received: December 12, 2022
Peer-review started: December 12, 2022
First decision: January 5, 2023
Revised: January 17, 2023
Accepted: February 16, 2023
Article in press: February 16, 2023
Published online: March 27, 2023
Processing time: 105 Days and 4.4 Hours
ARTICLE HIGHLIGHTS
Research background

As an important base in DNA demethylation, 5-hydroxymethylcytosine (5hmC) is also involved in epigenetic regulation, specifically in the assembly of chromosomes and the regulation of gene expression. However, the mechanism of action of 5hmC in hepatitis B surface antigen (HBsAg)-positive carriers and during the transition from cirrhosis to liver cancer remains unclear.

Research motivation

This study investigated the relationship between HBsAg-positive carriers, patients with cirrhosis, and patients with hepatocellular carcinoma using their serum samples and to identify potential genes and signaling pathways of DNA hydroxymethylation in order to understand the possible developmental mechanisms.

Research objectives

Using 5hmC sequencing technology, we analyzed the differentially expressed genes (DEGs) of HBsAg-positive carriers, patients with liver cirrhosis, and patients with liver cancer. The function of DEGs was further elucidated to explore the differences and similarities in gene hydroxymethylation and the regulatory role of signaling pathways in these groups.

Research methods

Using 5hmC DNA sequencing technology, we detected the expression profile of the samples, and the DEGs modified by DNA hydroxymethylation were screened. Bioinformatic analysis was used to enrich the DEGs.

Research results

The 5hmC DNA sequencing results showed that 30 genes were upregulated and 2 genes were downregulated in patients with hepatocellular carcinoma compared with HBsAg positive carriers. Further, 17 genes were upregulated and 3 genes were downregulated in hepatocellular carcinoma, compared with cirrhosis. Abnormal secretion of bile and insulin in tumor cells may promote or symbolize the occurrence and development of liver cancer. SLC2A2 and PCK1 are the central nodes of the differential genes, which may be most closely related to the occurrence of liver cancer. FABP1, APOC3, SI, KRT20, SLC5A1, SLC10A2, RBP2, and AKR1B10 may be the key genes in the protein regulatory network that play a regulatory role through 5hmC modification.

Research conclusions

The occurrence and development of liver cancer are related to several 5hmC-modified pathway genes and metabolic pathways, which may be potential therapeutic targets to prevent the progression of liver cancer in hepatitis B carriers.

Research perspectives

The differences and similarities in gene hydroxymethylation in HBsAg positive carriers, patients with cirrhosis, and patients with liver cancer and the regulatory role of signaling pathways were revealed by 5hmC sequencing technology.