Observational studyHepatology (Baltimore, Md.)2021
DNA Methylation Profiling of Human Hepatocarcinogenesis.
Observational study in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 114 citations in OpenAlex.
- Liquid biopsy-based multi-omics approach for early detection of hepatocellular carcinoma (ASCEND-Hep): a multiphase prospective development and validation study.BMC medicine · 2026Article
- A multi-centre, prospective trial of a methylation-based liquid biopsy for early detection of liver cancer in high-risk populations.Clinical and translational medicine · 2026Article
- Development and validation of a high-confidence diagnostic model integrating ctDNA methylation and serum biomarkers for early-stage hepatocellular carcinoma detection.Molecular biomedicine · 2026Article
- Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance.Human mutation · 2026Review
- Putative Imprinting Control Regions with Aberrant Blood-Based DNA Methylation are Associated with Hepatocellular Carcinoma Risk.Journal of hepatocellular carcinoma · 2026Article
- Epigenetic silencing ofFrontiers in genetics · 2026Article
- The oncogenic role of BCL2L12 associated with immune status in the prognosis of human hepatocellular carcinoma.Die Naturwissenschaften · 2025Article
- EZH2 expression in hepatocellular carcinoma and its relationship with circadian rhythm-related genes.Scientific reports · 2025Article
- Integration of RASSF1A and TSPYL5 methylation and AFP protein as plasma biomarker for hepatocellular carcinoma diagnosis.Journal of cancer research and clinical oncology · 2025Article
- STRIP2 promotes hepatocellular carcinoma progression and immune evasion: a potential prognostic biomarker and therapeutic target.Journal of gastrointestinal oncology · 2025Article
- Multi-omic analysis reveals elevated BRI3BP expression associated with hepatocellular carcinoma progression and poor prognosis.Scientific reports · 2025Article
- Exploration of signature-related FAM genes and correlation between FAM50A expression and the pathogenesis and prognosis of hepatocellular carcinoma.Translational cancer research · 2025Article
- Review
- A comparison of hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma: a bioinformatics analysis.Translational cancer research · 2025Article
- Clinical performance evaluation of a plasma dual-target methylation test for the detection of primary liver cancer: a multicenter study.Clinical epigenetics · 2025Observational
- METTL3 knockout accelerates hepatocarcinogenesis via inhibiting endoplasmic reticulum stress response.FEBS open bio · 2025Article
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- HBV sequence integrated to enhancer acting as oncogenic driver epigenetically promotes hepatocellular carcinoma development.Journal of experimental & clinical cancer research : CR · 2025Article
- Genome-Wide Methylation Sequencing to Identify DNA Methylation Markers for Early-stage Hepatocellular Carcinoma in Liver and Blood.Journal of experimental & clinical cancer research : CR · 2025Article
- Metabolomic liquid biopsy dynamics predict early-stage HCC and actionable candidates of human hepatocarcinogenesis.JHEP reports : innovation in hepatology · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
BACKGROUND AND
aimsMutations in TERT (telomerase reverse transcriptase) promoter are established gatekeepers in early hepatocarcinogenesis, but little is known about other molecular alterations driving this process. Epigenetic deregulation is a critical event in early malignancies. Thus, we aimed to (1) analyze DNA methylation changes during the transition from preneoplastic lesions to early HCC (eHCC) and identify candidate epigenetic gatekeepers, and to (2) assess the prognostic potential of methylation changes in cirrhotic tissue. APPROACH AND
resultsMethylome profiling was performed using Illumina HumanMethylation450 (485,000 cytosine-phosphateguanine, 96% of known cytosine-phosphateguanine islands), with data available for a total of 390 samples: 16 healthy liver, 139 cirrhotic tissue, 8 dysplastic nodules, and 227 HCC samples, including 40 eHCC below 2cm. A phylo-epigenetic tree derived from the Euclidean distances between differentially DNA-methylated sites (n = 421,997) revealed a gradient of methylation changes spanning healthy liver, cirrhotic tissue, dysplastic nodules, and HCC with closest proximity of dysplasia to HCC. Focusing on promoter regions, we identified epigenetic gatekeeper candidates with an increasing proportion of hypermethylated samples (beta value > 0.5) from cirrhotic tissue (<1%), to dysplastic nodules (≥25%), to eHCC (≥50%), and confirmed inverse correlation between DNA methylation and gene expression for TSPYL5 (testis-specific Y-encoded-like protein 5), KCNA3 (potassium voltage-gated channel, shaker-related subfamily, member 3), LDHB (lactate dehydrogenase B), and SPINT2 (serine peptidase inhibitor, Kunitz type 2) (all P < 0.001). Unsupervised clustering of genome-wide methylation profiles of cirrhotic tissue identified two clusters, M1 and M2, with 42% and 58% of patients, respectively, which correlates with survival (P < 0.05), independent of etiology.
conclusionsGenome-wide DNA-methylation profiles accurately discriminate the different histological stages of human hepatocarcinogenesis. We report on epigenetic gatekeepers in the transition between dysplastic nodules and eHCC. DNA-methylation changes in cirrhotic tissue correlate with clinical outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.