Proteomics in the diagnosis of hepatocellular carcinoma: focus on high risk hepatitis B and C patients

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The high morbidity rate associated with this cancer is mainly linked to the late diagnosis, when therapy is no longer effective and this is particularly true for high risk patients, such as hepatitis B and C infected individuals. A biomarker can be defined as a substance, found in an increased amount in the body fluids, such as blood, which can indicate the presence of liver cancer. Current screening methodologies for liver cancer in at-risk patients rely on measuring the serum level of alpha-fetoprotein (AFP), a biomarker, as well as ultrasound imaging. AFP's sensitivity is very limited since many other liver diseases can result in a very high blood level of AFP similar to that observed in HCC. In addition, AFP is not always elevated in the early stages of cancer development, when therapy is mostly effective. Imaging, on the other hand, depends to a large extent on the operator. Therefore, better diagnostic methods are needed to increase the survival rate in liver cancer patients. Proteomics can be simply defined as the protein expression of the genome; and protein expression can vary depending on the biological state. Antibody microarrays can scan for multiple targets (antigens) within the tissue or in the circulation. This technology is still in its infancy and has great potential as a diagnostic tool for hepatitis liver cancer patients. Another proteomic approach is mass spectrometry, which can detect proteins and present them as charged species (ions). The mass spectrometric technique termed SELDI (surface enhanced laser desorption ionization), releases proteins in a sample from a capturing surface that can specifically bind groups of proteins which share common features (hydrophobic, negatively charged, etc.) and the expression of thousands of proteins can be monitored simultaneously. Proteomic profiles of hepatitis patients, liver cancer patients and healthy individuals can be established and evaluated for diagnosis. Elevated proteins can further be isolated and identified using the well-established mass spectrometric protein identification methods. In this article, the technological SELDI mass spectrometry and antibody microarrays are presented at the basic level. In addition, the current state of the novel liver cancer diagnostic methods (and biomarkers) that have been evaluated with focus on high risk hepatitis B and C patients using proteomic approaches are reviewed and highlighted.