ArticleHepatology research : the official journal of the Japan Society of Hepatology2015
Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis.
Article in Hepatology research : the official journal of the Japan Society of Hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 34 citations in OpenAlex.
- Advances in Epigenomic Sequencing and Their Applications in Cancer Diagnostics.Precision chemistry · 2025Review
- MethMarkerDB: a comprehensive cancer DNA methylation biomarker database.Nucleic acids research · 2024Article
- Diagnosis of the Initial Stage of Hepatocellular Carcinoma: A Review.Current pharmaceutical design · 2024Review
- Impact of Cell-Debris and Room-Temperature Storage on Urine Circulating Tumor DNA from Hepatocellular Carcinoma.The Journal of molecular diagnostics : JMD · 2023Article
- Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians.Cancer cell international · 2023Review
- Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma.Molecular oncology · 2022Article
- Detection ofDiagnostics (Basel, Switzerland) · 2021Article
- Article
- Advances in the early diagnosis of hepatocellular carcinoma.Genes & diseases · 2020Review
- Methylation Dynamics ofCancers · 2019Review
- Urine-Based Liquid Biopsy for Nonurological Cancers.Genetic testing and molecular biomarkers · 2019Review
- Identification of Cross Talk between FoxM1 and RASSF1A as a Therapeutic Target of Colon Cancer.Cancers · 2019Article
- RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2019Article
- Using Illumina Infinium HumanMethylation 450K BeadChip to explore genome‑wide DNA methylation profiles in a human hepatocellular carcinoma cell line.Molecular medicine reports · 2018Article
- Liquid biopsies for hepatocellular carcinoma.Translational research : the journal of laboratory and clinical medicine · 2018Review
- Analysis of DNA methylation in cancer: location revisited.Nature reviews. Clinical oncology · 2018Review
- Development and Evaluation of Novel Statistical Methods in Urine Biomarker-Based Hepatocellular Carcinoma Screening.Scientific reports · 2018Article
- Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma.Hepatoma research · 2017Article
- Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics.Hepatology international · 2017Review
- The Correlation Relationship between P14ARF Gene DNA Methylation and Primary Liver Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
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11 authors at 6 institutions in 2 countries.
Funding
Abstract
aimAberrant methylation of the promoter, P2, and the first exon, E1, regions of the tumor suppressor gene RASSF1A, have been associated with hepatocellular carcinoma (HCC), albeit with poor specificity. This study analyzed the methylation profiles of P1, P2 and E1 regions of the gene to identify the region of which methylation most specifically corresponds to HCC and to evaluate the potential of this methylated region as a biomarker in urine for HCC screening.
methodsBisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays were performed to compare methylation of the 56 CpG sites in regions P1, P2 and E1 in DNA isolated from normal, hepatitic, cirrhotic, adjacent non-HCC, and HCC liver tissue and urine samples for the characterization of hypermethylation of the RASSF1A gene as a biomarker for HCC screening.
resultsIn tissue, comparing HCC (n = 120) with cirrhosis and hepatitis together (n = 70), methylation of P1 had an area under the receiver operating characteristics curve (AUROC) of 0.90, whereas methylation of E1 and P2 had AUROC of 0.84 and 0.72, respectively. At 90% sensitivity, specificity for P1 methylation was 72.9% versus 38.6% for E1 and 27.1% for P2. Methylated P1 DNA was detected in urine in association with cirrhosis and HCC. It had a sensitivity of 81.8% for α-fetoprotein negative HCC.
conclusionAmong the three regions analyzed, methylation of P1 is the most specific for HCC and holds great promise as a DNA marker in urine for screening of cirrhosis and HCC.
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