Pharmacological unmasking microarray approach-based discovery of novel DNA methylation markers for hepatocellular carcinoma

Namhee Jung, Jae Kyung Won, Baek-Hui Kim, Kyung Suk Suh, Ja June Jang, Gyeong Hoon Kang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

DNA methylation is one of the main epigenetic mechanisms and hypermethylation of CpG islands at tumor suppressor genes switches off these genes. To find novel DNA methylation markers in hepatocellular carcinoma (HCC), we performed pharmacological unmasking (treatment with 5-aza-2'-deoxycytidine or trichostatin A) followed by microarray analysis in HCC cell lines. Of the 239 promoter CpG island loci hypermethylated in HCC cell lines (as revealed by methylation-specific PCR), 221 loci were found to be hypermethylated in HCC or nonneoplastic liver tissues. Thirty-three loci showed a 20% higher methylation frequency in tumors than in adjacent nonneoplastic tissues. Correlation of individual cancer-related methylation markers with clinicopathological features of HCC patients (n=95) revealed that the number of hypermethylated genes in HCC tumors was higher in older than in younger patients. Univariate and multivariate survival analysis revealed that the HIST1H2AE methylation status is closely correlated with the patient's overall survival (P=0.022 and P=0.010, respectively). In conclusion, we identified 221 novel DNA methylation markers for HCC. One promising prognostic marker, HIST1H2AE, should be further validated in the prognostication of HCC patients.

Original languageEnglish
Pages (from-to)594-604
Number of pages11
JournalJournal of Korean Medical Science
Volume27
Issue number6
DOIs
Publication statusPublished - 2012 Jun 1
Externally publishedYes

Keywords

  • Carcinoma
  • CpG islands
  • DNA methylation
  • Hepatocellular
  • Microarray
  • Prognosis

ASJC Scopus subject areas

  • Medicine(all)

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