Increased expression of ZBP-89 and its prognostic significance in hepatocellular carcinoma

Histopathology. 2012 Jun;60(7):1114-24. doi: 10.1111/j.1365-2559.2011.04136.x. Epub 2012 Feb 28.

Abstract

Aims: ZBP-89 plays a role in cell growth and death. Its expression in hepatocellular carcinoma (HCC) is not well documented. This study aimed to analyse ZBP-89 expression in HCC.

Methods and results: We examined ZBP-89 expression in five HCC cell lines and 182 HCC tissue samples by reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunofluorescence staining. Our results showed that the expression of ZBP-89 was higher in HCC than adjacent non-tumour liver, at both mRNA and protein levels. ZBP-89 was localized in the nucleus in most HCC tissue samples, but was found in the cytoplasm in 11.5% of cases. Patient survival in those tumours showing high ZBP-89 expression was better than in those with low expression. High ZBP-89 expression tended to be more common in World Health Organization (WHO) grade I than grades II-IV HCC. There was a significant association between HBV positivity and high ZBP-89 expression. Colony formation was reduced dramatically in those HCC cell lines in which ZBP-89 overexpression was demonstrated; this appeared to correlate with increased apoptosis, inferred by finding elevated levels of cleaved poly(ADP-ribose)polymerases (PARP), the probable mechanisms for which may involve increased p53 or p21 expression.

Conclusions: ZBP-89 has anti-tumour properties and is a potential biomarker for prognosis of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Tumor Stem Cell Assay
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Transcription Factors
  • ZNF148 protein, human
  • Poly(ADP-ribose) Polymerases