Gel-based proteomics of liver cancer progression in rat

Biochim Biophys Acta. 2011 Oct;1814(10):1367-76. doi: 10.1016/j.bbapap.2011.05.018. Epub 2011 Jun 6.


A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n=18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular carcinoma (HCC) and we identify novel candidate proteomic aberrations for further analysis in human HCC. In particular, increased levels of HSP70, HSP90, AKR1B1, AKR7A3, GCLM, ANXA5, VDBP, RGN and SULT1E1 were associated specifically with rat hepatomas, or with liver cancer progression in rat. In addition, we examine an integrated gel-based workflow for analysis of protein post-translational modifications (PTMs) and microtubule-association. We highlight differential PTM and localization of HSP60 as an interesting target for further analysis in liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / metabolism
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism
  • Proteomics / methods*
  • Rats
  • Rats, Inbred F344
  • Two-Dimensional Difference Gel Electrophoresis


  • Microtubule-Associated Proteins
  • Phosphoproteins