Gel-based proteomics of liver cancer progression in rat

Jakob Albrethsen, Leah M. Miller, Phyllis M. Novikoff, Ruth H. Angeletti

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1367-1376
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1814
Issue number10
DOIs
StatePublished - Oct 1 2011

Keywords

  • Biomarker
  • HSP60
  • Inflammation
  • Liver cancer
  • Post-translational modification
  • Proteomics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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