ArticleClinical epigenetics2022
Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Genome-wide DNA methylation profiling during metabolic dysfunction-associated steatohepatitis-related hepatocarcinogenesis in patients in Japan and the United States.Scientific reports · 2026Article
- Putative Imprinting Control Regions with Aberrant Blood-Based DNA Methylation are Associated with Hepatocellular Carcinoma Risk.Journal of hepatocellular carcinoma · 2026Article
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- Label-Free Surface-Enhanced Raman Scattering for Genomic DNA Cytosine Methylation Reading.Molecules (Basel, Switzerland) · 2025Article
- Genome-Wide DNA Methylation Markers Associated With Metabolic Liver Cancer.Gastro hep advances · 2025Article
- Molecular pathological approach to cancer epigenomics and its clinical application.Pathology international · 2024Review
- Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Impact of Surgical Margin Width on Prognosis Following Resection of Hepatocellular Carcinoma Varies on the Basis of Preoperative Alpha-Feto Protein and Tumor Burden Score.Annals of surgical oncology · 2023Article
- Loss of PPARα function promotes epigenetic dysregulation of lipid homeostasis driving ferroptosis and pyroptosis lipotoxicity in metabolic dysfunction associated Steatotic liver disease (MASLD).Frontiers in molecular medicine · 2023Article
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn recent years, non-alcoholic steatohepatitis (NASH) has become the main cause of hepatocellular carcinoma (HCC). As a means of improving the treatment of NASH-related HCCs based on early detection, this study investigated the feasibility of carcinogenic risk estimation in patients with NASH.
resultsNormal liver tissue (NLT), non-cancerous liver tissue showing histological findings compatible with non-alcoholic fatty liver from patients without HCC (NAFL-O), non-cancerous liver tissue showing NASH from patients without HCC (NASH-O), non-cancerous liver tissue showing non-alcoholic fatty liver from patients with HCC (NAFL-W), non-cancerous liver tissue showing NASH from patients with HCC (NASH-W) and NASH-related HCC were analyzed. An initial cohort of 171 tissue samples and a validation cohort of 55 tissue samples were used. Genome-wide DNA methylation screening using the Infinium HumanMethylation450 BeadChip and DNA methylation quantification using high-performance liquid chromatography (HPLC) with a newly developed anion-exchange column were performed. Based on the Infinium assay, 4050 CpG sites showed alterations of DNA methylation in NASH-W samples relative to NLT samples. Such alterations at the precancerous NASH stage were inherited by or strengthened in HCC samples. Receiver operating characteristic curve analysis identified 415 CpG sites discriminating NASH-W from NLT samples with area under the curve values of more than 0.95. Among them, we focused on 21 CpG sites showing more than 85% specificity, even for discrimination of NASH-W from NASH-O samples. The DNA methylation status of these 21 CpG sites was able to predict the coincidence of HCC independently from histopathological findings such as ballooning and fibrosis stage. The methylation status of 5 candidate marker CpG sites was assessed using a HPLC-based system, and for 3 of them sufficient sensitivity and specificity were successfully validated in the validation cohort. By combining these 3 CpG sites including the ZC3H3 gene, NAFL-W and NASH-W samples from which HCCs had already arisen were confirmed to show carcinogenic risk with 95% sensitivity in the validation cohort.
conclusionsAfter a further prospective validation study using a larger cohort, carcinogenic risk estimation in liver biopsy specimens of patients with NASH may become clinically applicable using this HPLC-based system for quantification of DNA methylation.
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