Mapping of the Serum Proteome of Hepatocellular Carcinoma Induced by Targeted Overexpression of Epidermal Growth Factor to Liver Cells of Transgenic Mice

Abstract

Epidermal growth factor (EGF) is an important mitogen for hepatocytes. Its targeted overexpression induced hepatocellular carcinomas (HCC), as recently reported by us (Borlak et al. 2005). Early detection of disease is essential for successful therapy and overall survival. Here we describe our efforts in identifying serum biomarkers of liver cancer in a transgenic disease model that mimics effectively the consequence of exaggerated EGF signaling. We report a reference 2-DE map of mouse serum proteins. About 180 proteins were detected per gel and 130 proteins were identified by 2-DE-MALDI-MS analysis. We compared serum proteins of healthy nontransgenic and HCC tumor-bearing mice and identified 25 regulated proteins, of which n = 7 reached statistical significance ( p < 0.05). Furthermore, we identified several fragments of fibrinogens and of the alpha-2-macroglobulin to be disease-associated. We also found immunoglobulins to be repressed or absent in serum samples of tumor-bearing mice, and this included, among others, the Ig K and L class. In contrast, amyloid component P and apolipoprotein M were highly significantly increased by 10- and 8-fold, respectively, in serum samples of HCC mice. Overall, our findings provide a rationale for further clinical evaluation of the herein identified biomarker candidates.