ArticleEnvironmental health and preventive medicine2020
Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes.
Article in Environmental health and preventive medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Integrated Bioinformatics and Multi-Omics Analysis of ZBTB40 Expression, Prognostic Relevance, and Regulatory Networks in Hepatocellular Carcinoma.Medicina (Kaunas, Lithuania) · 2026Article
- KIF15 (Kinesin-12): molecular biology, physiological functions, and roles in disease.Journal of cancer research and clinical oncology · 2026Review
- A Bioinformatics and Wet-Lab-Based Pipeline IdentifiesInternational journal of molecular sciences · 2026Article
- KIF4A in disease pathogenesis and therapeutics: from molecular mechanisms to clinical translation.Biology direct · 2025Review
- Macrophage polarization in hepatocellular carcinoma: a lncRNA-centric perspective on tumor progression and metastasis.Clinical and experimental medicine · 2025Review
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- Multi-Omics Integration for Liver Cancer Using Regression Analysis.Current issues in molecular biology · 2024Article
- A pan-cancer analysis of the oncogenic role of ERCC6L.BMC cancer · 2022Article
- Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma.Biomedicines · 2022Review
- INK4 cyclin-dependent kinase inhibitors as potential prognostic biomarkers and therapeutic targets in hepatocellular carcinoma.Bioscience reports · 2022Article
- Article
- Article
- Bioinformatic analyses of hydroxylated polybrominated diphenyl ethers toxicities on impairment of adrenocortical secretory function.Environmental health and preventive medicine · 2022Article
- CDKN2A is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.Bioscience reports · 2021Article
- Identification by Comprehensive Bioinformatics Analysis of KIF15 as a Candidate Risk Gene for Triple-Negative Breast Cancer.Cancer management and research · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundVarious treatments for hepatocellular carcinoma (HCC) are utilized in clinical practice; however, the prognosis is still poor on account of high recurrence rates. DNA methylation levels of CpG islands around promoters (promoter CpGis) inversely regulate gene expression and closely involved in carcinogenesis. As a new strategy, several chemicals globally inhibiting DNA methylation have been developed aiming at reducing DNA methylation levels and maintaining the expression of tumor suppressor genes. On the other hand, since these drugs nonspecifically modify DNA methylation, they can cause serious adverse effects. In order to ameliorate the methods by targeting specific CpGs, information of cancer-related genes that are regulated by DNA methylation is required.
methodsWe searched candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and which are involved in HCC cases. To do so, we first identified genes whose expression were changed in HCC by comparing gene expressions of 371 HCC tissues and 41 non-tumor tissues using the Cancer Genome Atlas (TCGA) database. The genes were further selected for poor prognosis by log-rank test of Kaplan-Meier plot and for cancer relevance by Pubmed search. Expression profiles of upregulated genes in HCC tissues were assessed by Gene Ontology (GO) analysis. Finally, using DNA methylation data of TCGA database, we selected genes whose promoter DNA methylation levels were inversely correlated with gene expression.
resultsWe found 115 genes which were significantly up- or downregulated in HCC tissues and were associated with poor prognosis and cancer relevance. The upregulated genes were significantly enriched in cell division, cell cycle, and cell proliferation. Among the upregulated genes in HCC, we identified hypomethylation of CpGis around promoters of FANCB, KIF15, KIF4A, ERCC6L, and UBE2C. In addition, TCGA data showed that the tumor suppressor gene P16 is unexpectedly overexpressed in many types of cancers.
conclusionsWe identified five candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and associate with cancer cases and poor prognosis in HCC. Modification of site-specific DNA methylation of these genes enables a different approach for HCC treatment with higher selectivity and lower adverse effects.
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