ORIGINAL RESEARCH article

Front. Med.

Sec. Hepatobiliary Diseases

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1520380

This article is part of the Research TopicGenomic Dissection and Therapy Development in Liver CancerView all articles

DNA Methylation-Driven Genes in Hepatocellular Carcinoma Patients: Insights into Immune Infiltration and Prognostic Implications

Provisionally accepted
Zhi  ZhangZhi Zhang1Tongling  ZhaoTongling Zhao2Weida  MengWeida Meng1Jiahao  ChenJiahao Chen1Chengyi  HeChengyi He1Xing  SunXing Sun3Huang  HaiHuang Hai1*
  • 1Guangxi Medical University Affliated Wuming Hospital, Nanning, China
  • 2Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
  • 3The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China

The final, formatted version of the article will be published soon.

Background: Hepatocellular carcinoma (HCC) poses a significant global burden as a highly prevalent and life-threatening malignant tumor that endangers human life and well-being. The purpose of this study was to examine how DNA methylation-driven genes impact the prognosis of HCC patients.Methods: DEGs from The Cancer Genome Atlas, GSE76427, GSE25097 and GSE14520 datasets were collected to perform differential expression analysis between HCC patients and controls. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to create coexpression modules for the DEGs. Then, ssGSEA was employed to investigate the infiltration of immune cells in HCC. Enrichment analysis and methylation were carried out for the module genes. We utilized Kaplan‒Meier survival analysis to assess patient prognosis.Results: Eight coexpression modules were identified via WGCNA for 1927 upregulated and 1231 downregulated DEGs, after which the hub genes of the modules were identified. Module 5 had high immune infiltration, and the hub gene SCAMP3 was positively associated with Tcm. Module 3 exhibited a low level of immune infiltration, and the expression of the hub gene HCLS1 was negatively correlated with T cells and dendritic cells. Furthermore, we obtained five hub genes (BOP1, BUB1B, NOTCH3, SCAMP3 and SNRPD2) as methylation-driven genes. BOP1 and BUB1B were found to be correlated with unfavorable overall survival in patients with HCC.Conclusion: HCLS1 and SCAMP3 are associated with immunity, whereas BOP1 and BUB1B are modified by methylation and may serve as prognostic markers for HCC.

Keywords: Hepatocellular Carcinoma, bioinformatics, TCGA, WGCNA, prognosis

Received: 31 Oct 2024; Accepted: 09 Apr 2025.

Copyright: © 2025 Zhang, Zhao, Meng, Chen, He, Sun and Hai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Huang Hai, Guangxi Medical University Affliated Wuming Hospital, Nanning, China

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