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Cited by 196Epigenetics and DNA MethylationCancer Genomics and DiagnosticsHepatocellular Carcinoma Treatment and Prognosis

Genome-wide DNA methylation profiles in hepatocellular carcinoma

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Shen, Jing, Wang, Shuang, Zhang, Yu-Jing, Kappil, Maya, Wu, Hui-Chen, Kibriya, Muhammad G., Wang, Qiao, Jasmine, Farzana +5 more·2012·Hepatology
DOI 10.1002/hep.25569PMC PMC3330167
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Abstract

Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA before HCC diagnosis. To identify, with a genome-wide approach, additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent nontumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays (Illumina, Inc., San Diego, CA) that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor, compared to nontumor tissues. Array data were validated with pyrosequencing in a subset of five of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37%-63% of cases had detectable hypermethylated DNA (≥5% methylation) for these five genes individually. At least one of these genes was hypermethylated in 87% of the cases, suggesting that measurement of DNA methylation in plasma samples is feasible. Conclusion: The panel of methylated genes indentified in the current study will be further tested in a large cohort of prospectively collected samples to determine their utility as early biomarkers of HCC.

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  • The role of epigenetic dysregulation in driving the aberrant activity of CREs and retrotransposons in HCC remains incompletely understood.

    “the role of epigenetic dysregulation in driving the aberrant activity of CREs and retrotransposons in HCC remains incompletely understood50–52,93.”

    From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [52]

    The Introduction links genetic and epigenetic aberrations to HCC, and the Results describe altered DNA methylation in HCC tissue. The paper does not address whether epigenetic dysregulation drives aberrant activity of cis-regulatory elements or retrotransposons, or whether that role remains incompletely understood (searched for CREs, enhancers, and retrotransposons). (LLM, conf=0.78)

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Authors
Shen, J., Wang, S., Zhang, Y.-J., Kappil, M., Wu, H.-C., Kibriya, M. G., Wang, Q., Jasmine, F., Ahsan, H., Lee, P.-H., Yu, M.-W., Chen, C.-J., & Santella, R. M.
Affiliations
  • Columbia University (US)
  • University of Chicago (US)
  • National Taiwan University (TW)
Corresponding author
Santella, Regina M.
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-06
Volume
55
Issue
6
Pages
1799-1808
ISSN
0270-9139 (ISSN-L)
DOI
10.1002/hep.25569
PMC
PMC3330167
OpenAlex
W2031842191
Cited by
196
References
0
Citations by year
2026: 4 · 2025: 10 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 12 · 2019: 13 · 2018: 16 · 2017: 15 · 2016: 29 · 2015: 15 · 2014: 24 · 2013: 14 · 2012: 11
FWCI
8.22
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1187 d)
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (CA013696, ES009089)
  • National Cancer Institute (R03CA150140, P30CA013696)
  • National Institute of Environmental Health Sciences (R01ES005116, P30ES009089)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
hepatocellular carcinoma, DNA methylation, hypermethylation, hypomethylation, CpG sites, plasma DNA, early diagnosis, tumor markers
MeSH terms
Adult, Aged, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, CpG Islands, DNA Methylation, Genome-Wide Association Study

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