Proteomic analysis of hepatitis B virus-associated hepatocellular carcinoma: Identification of potential tumor markers

Proteomics. 2005 Mar;5(4):1125-39. doi: 10.1002/pmic.200401141.


Hepatocellular carcinoma (HCC) is a malignancy of both underdeveloped and developing countries. Proteomes of ten pairs of clinical hepatitis B virus associated HCC tissue samples were obtained by high resolution two-dimensional gel electrophoresis. Comprehensive analyses of proteins associated with B-type HCC were focused on total differentially expressed proteins (> or = two-fold increase or decrease, Student's t-test, p < 0.05) from one pair of samples. Protein identification was done by peptide mass fingerprinting with matrix assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Comparative analyses of proteins associated with B-type HCC included repeat statistics in ten cases. A total of 100 protein spots, corresponding to 80 different gene products, were identified. Proteins whose expression levels were different by more than 2-fold in at least 50% of the cases (five of ten cases) were further analyzed and 45 proteins were selected out as candidates for HCC-associated proteins. Western blotting further validated up-regulated expressions of two candidate proteins in tumor tissues: proliferating cell antigen and stathmin 1. This comprehensive and comparative analyses of proteins associated with B-type HCC could provide useful molecular markers for diagnostics and prognostics and for therapeutic targets. The physiological significance of the differential expressions for several candidate proteins are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Biomarkers, Tumor*
  • Blotting, Western
  • Carcinoma, Hepatocellular / complications*
  • Carcinoma, Hepatocellular / virology*
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Computational Biology / methods*
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Expression Regulation, Viral*
  • Hepatitis B / complications*
  • Hepatitis B virus / metabolism*
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Mass Spectrometry / methods*
  • Microtubule Proteins / biosynthesis
  • Middle Aged
  • Molecular Sequence Data
  • Phosphoproteins / biosynthesis
  • Proliferating Cell Nuclear Antigen / biosynthesis
  • Protein Isoforms
  • Proteomics / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Stathmin
  • Up-Regulation


  • Biomarkers, Tumor
  • Microtubule Proteins
  • Phosphoproteins
  • Proliferating Cell Nuclear Antigen
  • Protein Isoforms
  • STMN1 protein, human
  • Stathmin