DNA binding protein A expression and methylation status in hepatocellular carcinoma and the adjacent tissue

Int J Oncol. 2012 Mar;40(3):789-97. doi: 10.3892/ijo.2011.1282. Epub 2011 Dec 6.

Abstract

We investigated the expression and promoter methylation of dbpA in human hepatocellular carcinoma (HCC) and examined their correlation with clinicopathological features. In 96 paired samples of HCC and adjacent non-tumorous liver, and 10 normal liver specimens, dbpA mRNA was quantified by real-time RT-PCR, and promoter methylation was examined by methylation-specific polymerase chain reaction and bisulfite sequencing. The results showed that dbpA mRNA expression levels were higher in HCC compared to corresponding non-tumor tissues (P<0.01) and higher in non-virus-associated HCC compared to virus-associated cases (P<0.01). dbpA promoter was methylated in 37.7% of HCC samples and the promoter methylation was significantly correlated with the low expression of dbpA in non-virus-associated HCC (P<0.01), but not in virus-associated HCC. Surprisingly, poor prognosis was more significantly associated with high dbpA expression in non-tumorous liver (P=0.018) but not with that in HCC. Non-tumorous tissues consist of chronic hepatitis or liver cirrhosis, and these conditions are the background of hepatocarcinogenesis, defined as the hypercarcinogenic state. Our results suggest that the high expression of dbpA in the hypercarcinogenic state is an indicator of poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins / biosynthesis
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • CpG Islands
  • DNA Methylation*
  • Female
  • Heat-Shock Proteins / biosynthesis
  • Heat-Shock Proteins / genetics*
  • Hepatitis, Chronic / genetics
  • Hepatitis, Chronic / pathology
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Prognosis
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Heat-Shock Proteins
  • RNA, Messenger
  • YBX3 protein, human