DNA damage sensor γ -H2AX is increased in preneoplastic lesions of hepatocellular carcinoma

ScientificWorldJournal. 2013:2013:597095. doi: 10.1155/2013/597095. Epub 2013 Mar 3.

Abstract

Background: Phosphorylated histone H2AX ( γ -H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ -H2AX in hepatocellular carcinoma (HCC), we measured the level of γ -H2AX in HCC, dysplastic nodule, and nontumorous liver diseases.

Methods: The level of γ -H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. results: All cases with chronic liver disease showed increased levels of γ -H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ -H2AX was above 50% and was inversely correlated with the histological grade. Mean γ -H2AX LI was the highest in dysplastic nodule (74.1 ± 22.1%), which was significantly higher than HCC (P < 0.005). Moreover, γ -H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5 ± 24.7%, from 5.1 to 96.0%, P < 0.005).

Conclusions: γ -H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism
  • Case-Control Studies
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • DNA Damage*
  • Female
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / metabolism
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / metabolism
  • Histones / metabolism*
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / metabolism
  • Liver Neoplasms / diagnosis
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • H2AX protein, human
  • Histones