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Disease Markers
Volume 17, Issue 3, Pages 179-189
http://dx.doi.org/10.1155/2001/963023

A Proteomic Approach for the Discovery of Early Detection Markers of Hepatocellular Carcinoma

Laura F. Steel,1 Taj S. Mattu,1 Anand Mehta,1 Holger Hebestreit,2 Raymond Dwek,2 Alison A. Evans,3 W. Thomas London,3 and Timothy Block1

1Department of Biochemistry and Molecular Pharmacology, Jefferson Center for Biomedical Research, Thomas Jefferson University, Doylestown, PA 18901, USA
2Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK
3Fox Chase Cancer Center, Philadelphia, PA 19101, USA

Received 31 October 2001; Accepted 31 October 2001

Copyright © 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.