DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications
BackgroundHepatocellular carcinoma (HCC) poses a significant global burden as a highly prevalent and life-threatening malignant tumor that endangers human life and wellbeing. The purpose of this study was to examine how DNA methylation-driven genes impact the prognosis of HCC patients.MethodsDiffere...
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Frontiers Media S.A.
2025-04-01
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| author | Zhi Zhang Tongling Zhao Weida Meng Jiahao Chen Chengyi He Xing Sun Hai Huang |
| author_facet | Zhi Zhang Tongling Zhao Weida Meng Jiahao Chen Chengyi He Xing Sun Hai Huang |
| author_sort | Zhi Zhang |
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| description | BackgroundHepatocellular carcinoma (HCC) poses a significant global burden as a highly prevalent and life-threatening malignant tumor that endangers human life and wellbeing. The purpose of this study was to examine how DNA methylation-driven genes impact the prognosis of HCC patients.MethodsDifferentially expressed genes 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.ResultsEight coexpression modules were identified via WGCNA for 1927 upregulated and 1,231 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.ConclusionHCLS1 and SCAMP3 are associated with immunity, whereas BOP1 and BUB1B are modified by methylation and may serve as prognostic markers for HCC. |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-823b30ebad1e4c7facce5c70992b769b2025-08-20T02:29:50ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-04-011210.3389/fmed.2025.15203801520380DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implicationsZhi Zhang0Tongling Zhao1Weida Meng2Jiahao Chen3Chengyi He4Xing Sun5Hai Huang6Department of Hepatobiliary Surger, Guangxi Medical University Affliated Wuming Hospital, Nanning, ChinaCollaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed by the Province and Ministry, Guangxi Medical University, Nanning, ChinaDepartment of Hepatobiliary Surger, Guangxi Medical University Affliated Wuming Hospital, Nanning, ChinaDepartment of Hepatobiliary Surger, Guangxi Medical University Affliated Wuming Hospital, Nanning, ChinaDepartment of Hepatobiliary Surger, Guangxi Medical University Affliated Wuming Hospital, Nanning, ChinaDepartment of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hepatobiliary Surger, Guangxi Medical University Affliated Wuming Hospital, Nanning, ChinaBackgroundHepatocellular carcinoma (HCC) poses a significant global burden as a highly prevalent and life-threatening malignant tumor that endangers human life and wellbeing. The purpose of this study was to examine how DNA methylation-driven genes impact the prognosis of HCC patients.MethodsDifferentially expressed genes 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.ResultsEight coexpression modules were identified via WGCNA for 1927 upregulated and 1,231 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.ConclusionHCLS1 and SCAMP3 are associated with immunity, whereas BOP1 and BUB1B are modified by methylation and may serve as prognostic markers for HCC.https://www.frontiersin.org/articles/10.3389/fmed.2025.1520380/fullhepatocellular carcinomabioinformaticsTCGAWGCNAprognosis |
| spellingShingle | Zhi Zhang Tongling Zhao Weida Meng Jiahao Chen Chengyi He Xing Sun Hai Huang DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications Frontiers in Medicine hepatocellular carcinoma bioinformatics TCGA WGCNA prognosis |
| title | DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications |
| title_full | DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications |
| title_fullStr | DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications |
| title_full_unstemmed | DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications |
| title_short | DNA methylation-driven genes in hepatocellular carcinoma patients: insights into immune infiltration and prognostic implications |
| title_sort | dna methylation driven genes in hepatocellular carcinoma patients insights into immune infiltration and prognostic implications |
| topic | hepatocellular carcinoma bioinformatics TCGA WGCNA prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1520380/full |
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