Comparative analysis of the liver and plasma proteomes as a novel and powerful strategy for hepatocellular carcinoma biomarker discovery.

The extraordinary developments made in the past decade in proteomic technologies, in particular in mass spectrometry, have enabled investigators to consider designing studies to search for diagnostic and therapeutic biomarkers by scanning complex proteome samples. We developed a method based on extensive fractionation of intact proteins, to comprehensively and quantitatively profile the liver and plasma proteomes in health and disease. We have applied this method to samples collected from patients with early hepatocellular carcinoma (HCC) and from patients with liver cirrhosis as well as to samples collected from three mouse models of HCC. This method allowed for the identification of proteins that differ in expression levels in liver tissue or in plasma with disease progression from liver fibrosis, cirrhosis or steatohepatitis to HCC. The comparative analysis of the liver and plasma proteomes generated from human and mouse specimens, constitutes a novel and powerful strategy for HCC biomarker discovery.