Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma

Siyu Fu, Teoman Deger, Ruben G. Boers, Joachim B. Boers, Michael Doukas, Joost Gribnau, Saskia M. Wilting, José D. Debes, Andre Boonstra

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aberrant DNA methylation changes have been reported to be associated with carcinogenesis in cirrhotic HCC, but DNA methylation patterns for these non-cirrhotic HCC cases were not examined. Therefore, we sought to investigate DNA methylation changes on non-cirrhotic HCC using reported promising DNA methylation markers (DMMs), including HOXA1, CLEC11A, AK055957, and TSPYL5, on 146 liver tissues using quantitative methylation-specific PCR and methylated DNA sequencing. We observed a high frequency of aberrant methylation changes in the four DMMs through both techniques in non-cirrhotic HCC compared to cirrhosis, hepatitis, and benign lesions (p < 0.05), suggesting that hypermethylation of these DMMs is specific to non-cirrhotic HCC development. Also, the combination of the four DMMs exhibited 78% sensitivity at 80% specificity with an AUC of 0.85 in discriminating non-cirrhotic HCC from hepatitis and benign lesions. In addition, HOXA1 showed a higher aberrant methylation percentage in non-cirrhotic HCC compared to cirrhotic HCC (43.3% versus 13.3%, p = 0.039), which was confirmed using multivariate linear regression (p < 0.05). In summary, we identified aberrant hypermethylation changes in HOXA1, CLEC11A, AK055957, and TSPYL5 in non-cirrhotic HCC tissues compared to cirrhosis, hepatitis, and benign lesions, providing information that could be used as potentially detectable biomarkers for these unusual HCC cases in clinical practice.

Original languageEnglish (US)
Article number4784
JournalCancers
Volume15
Issue number19
DOIs
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • AK055957
  • CLEC11A
  • DNA methylation markers
  • HOXA1
  • MeD-seq
  • TSPYL5
  • non-cirrhotic HCC
  • qMSP

PubMed: MeSH publication types

  • Journal Article

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