Affiliations: Department of Biochemistry and Molecular Pharmacology,
Jefferson Center for Biomedical Research, Thomas Jefferson University,
Doylestown, PA 18901, USA | Oxford Glycobiology Institute, University of Oxford,
Oxford OX1 3QU, UK | Fox Chase Cancer Center, Philadelphia, PA 19101,
USA
Abstract: Individuals chronically infected with hepatitis B or C virus (HBV,
HCV) are at high risk for the development of hepatocellular carcinoma (HCC),
with disease progression occurring relentlessly over many years. The diagnosis
of HCC usually occurs at late stages in the disease when there are few
effective treatment options and the prognosis for patients with HCC is very
poor. The long latency period, together with clearly identified at risk
populations, provide opportunities for earlier detection that will allow more
timely and effective treatment of this devastating cancer. We are using a
proteomic approach to test the hypothesis that changes in the amount of certain
serum polypeptides, or changes in their post-translational modifications, can
be used to predict the onset of HCC. Advances in the standardization of two
dimensional gel electrophoresis (2DE) coupled with computerized image analysis
now permit the reproducible resolution of thousands of polypeptides per run.
Serum polypeptides from individuals at different stages in the disease
continuum are being resolved by 2DE to identify those that change with disease
progression. Polypeptides found by this method can be further characterized by
mass spectrometry. In addition, the potential for changes in the glycan
structure of certain polypeptides to serve as a marker for disease progression
can be explored. The proteomic approach is expected to liberate us from the
need to "cherry pick" or guess the best biomarkers and let the data tell us
which are the best indicators of disease. Information may also be gleaned about
the pathobiology of the disease process.
