Hepatocellular carcinoma: From bedside to proteomics

Abstract

Hepatocellular carcinoma (HCC or hepatoma) is the most common primary cancer 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. Although 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 suitable 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 the treatment of HCC. Screening for these HCC proteins has been facilitated by 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 expression profiles of several hepatoma cell lines such as HepG2, Huh7, SK-Hep1, and Hep3B have been compared with normal liver, and nontransformed cell lines (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 the gene expression studies of HCC which are already underway. Efforts have also been directed at the proteome analysis of hepatic stellate cells, as these 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.

A decade?s studies on metastasis of hepatocellular carcinoma

“…Molecular cytogenetic information provided by CGH was claimed to be useful for estimating the prognosis of patients with HCC (Kusano et al 2002). Proteomics will be an important approach (Seow et al 2001;Kim et al2002), but complicated.…”

Altered protein expression at early-stage rat hepatic neoplasia

“…The biological function of annexin V (lipocortin V) is not known, although its properties include inhibition of phospholipase A2, vascular anticoagulation, and binding of glycosaminoglycans (22). A proteomic study in normal liver did not find annexin V in parenchymal hepatocytes but did find the protein in an unidentified population of small hepatic cells (60,61). The finding of annexin V in the liver with early nodules suggests that annexin V may be associated with populations of hepatic cells not usually present in normal liver and may indicate the beginning of the early pathology of liver cancer.…”

Hox B4 as potential marker of non-differentiated cells in human cervical cancer cells

“…New approaches integrate several technologies, such as high-throughput, protein separation, browser-based bioinformatics to identify the molecules participating in the disease processes (Lee et al 2005;Wu et al 2002;Adam et al 2001;Meehan et al 2002;Jones et al 2002;Somiari et al 2005;Petricoin et al 2002;Seow et al 2001). This field is being applied for CC studies at present (Tang et al 2007;Lin et al 2006;Bae et al 2005; Barba de la Rosa et al 2008).…”