ArticleBMC medicine2020
Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing.
Article in BMC medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Comprehensive molecular characterization of cfDNA as predictive and monitoring biomarkers in advanced gastric cancer receiving immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Review
- A comparison of hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma: a bioinformatics analysis.Translational cancer research · 2025Article
- Fragment dispersity index analysis of cfDNA fragments reveals chromatin accessibility and enables early cancer detection.Cell reports methods · 2025Article
- EM-DeepSD: A Deep Neural Network Model Based on Cell-Free DNA End-Motif Signal Decomposition for Cancer Diagnosis.Diagnostics (Basel, Switzerland) · 2025Article
- Circulating tumor DNA methylation detection as biomarker and its application in tumor liquid biopsy: advances and challenges.MedComm · 2024Review
- Cell-free DNA end characteristics enable accurate and sensitive cancer diagnosis.Cell reports methods · 2024Article
- Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.Molecular cancer · 2024Review
- Circulating cell-free DNA-based methylation pattern in plasma for early diagnosis of esophagus cancer.PeerJ · 2024Review
- Liquid Liver Biopsy for Disease Diagnosis and Prognosis.Journal of clinical and translational hepatology · 2023Review
- Gene body hypomethylation of pyroptosis-related genes NLRP7, NLRP2, and NLRP3 facilitate non-invasive surveillance of hepatocellular carcinoma.Functional & integrative genomics · 2023Article
- The Use of ctDNA in the Diagnosis and Monitoring of Hepatocellular Carcinoma-Literature Review.International journal of molecular sciences · 2023Review
- DNA methylation analysis explores the molecular basis of plasma cell-free DNA fragmentation.Nature communications · 2023Article
- Analysis of viral integration reveals new insights of oncogenic mechanism in HBV-infected intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma.Hepatology international · 2022Article
- Whole-genome circulating tumor DNA methylation landscape reveals sensitive biomarkers of breast cancer.MedComm · 2022Article
- Whole-genome bisulfite sequencing analysis of circulating tumour DNA for the detection and molecular classification of cancer.Clinical and translational medicine · 2022Article
- mRNA expression and epigenetic-based role of chromodomain helicase DNA-binding 5 in hepatocellular carcinoma.The Journal of international medical research · 2022Article
- Article
- Liquid Biopsy Using Cell-Free or Circulating Tumor DNA in the Management of Hepatocellular Carcinoma.Cellular and molecular gastroenterology and hepatology · 2022Review
- Mechanisms of DNA Methylation in Virus-Host Interaction in Hepatitis B Infection: Pathogenesis and Oncogenetic Properties.International journal of molecular sciences · 2021Review
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundCirculating cell-free DNA (cfDNA) methylation has been demonstrated to be a promising approach for non-invasive cancer diagnosis. However, the high cost of whole genome bisulfite sequencing (WGBS) hinders the clinical implementation of a methylation-based cfDNA early detection biomarker. We proposed a novel strategy in low-pass WGBS (~ 5 million reads) to detect methylation changes in circulating cell-free DNA (cfDNA) from patients with liver diseases and hepatocellular carcinoma (HCC).
methodsThe effective small sequencing depth were determined by 5 pilot cfDNA samples with relative high-depth WGBS. CfDNA of 51 patients with hepatitis, cirrhosis, and HCC were conducted using low-pass WGBS. The strategy was validated in an independent WGBS cohort of 32 healthy individuals and 26 early-stage HCC patients. Fifteen paired tumor tissue and buffy coat samples were used to characterize the methylation of hepatitis B virus (HBV) integration regions and genome distribution of cfDNA.
resultsA significant enrichment of cfDNA in intergenic and repeat regions, especially in previously reported HBV integration sites were observed, as a feature of cfDNA and the bias of cfDNA release. Methylation profiles nearby HBV integration sites were a better indicator for hypomethylation of tumor genome comparing to Alu and LINE (long interspersed nuclear element) repeats, and were able to facilitate the cfDNA-based HCC prediction. Hypomethylation nearby HBV integration sites (5 kb flanking) was detected in HCC patients, but not in patients with hepatitis and cirrhosis (Methyl
conclusionsHypomethylation around viral integration sites aids low-pass cfDNA WGBS to serve as a non-invasive approach for early HCC detection, and inspire future efforts on tumor surveillance for oncovirus with integration activity.
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