Hepatocellular carcinoma: From bedside to proteomics

Hepatocellular carcinoma (HCC or hepatoma) is the most common primary cance r of the liver. It is responsible for approximately one million deaths each year, mainly in underdeveloped and developing countries. The aetiological factors identified in the development of HCC included persistent infection by hepatitis B and hepatitis C viruses, and exposure to aflatoxins. Althoug h immunization can protect individuals from being infected by the hepatitis B virus, the early detection of HCC in those who have been infected by the virus remains a challenge. Thus most HCCs present late and are not suitabl e for curative treatment. Hence there is a tremendous interest and urgency to identify novel HCC diagnostic marker(s) for early detection, and tumour specific disease associated proteins as potential therapeutic targets in th e treatment of HCC. Screening for these HCC proteins has been facilitated b y proteomics, a key technology in the global analysis of protein expression and understanding gene function. Present and earlier proteome analyses of HCC have used predominantly experimental in vitro systems. The protein expr ession profiles of several hepatoma cell lines such as HepG2, Huh7, SK-Hep1 , and Hep3B have been compared with normal liver, and nontransformed cell l ines (Chang and WRL-68), while a comprehensive proteome analysis to create a protein database was carried out for the cell line HCC-M. In the future, proteome analyses utilizing tumour tissues, which reflect the pathological state of HCC more closely, will be undertaken. This work will complement th e gene expression studies of HCC which are already underway. Efforts have a lso been directed at the proteome analysis of hepatic stellate cells, as th ese cells play an important role in liver fibrosis. Since liver fibrosis is reversible but not cirrhosis, it is of considerable importance to identify therapeutic targets that can slow its progression.