CRH-BP as a possible diagnostic marker for Hepatocellular carcinoma

Abstract

Hepatocellular Carcinoma (HCC) is especially prevalent in parts of Asia and Africa. About 80% of people with hepatocellular carcinomas have cirrhosis. Chronic infection with the hepatitis B virus and hepatitis C virus also increases the risk of developing hepatocellular carcinoma. HCC is a difficult cancer to diagnose and thus treatment is usually administered too late. A previous microarray study done revealed 218 genes with potential to be diagnostic markers due to significant differential expression in tumour relative to non-tumor tissues. Corticotrophin-releasing hormone binding protein (CRH-BP) was one of these genes. It is a secreted protein that is associated with regulation of CRH. CRH-BP expression was down-regulated in HCC derived cell lines and clinical samples as measured by quantitative real-time PCR and regular RT-PCR. To explore the possible reason behind this down-regulation, MSP and 5-Aza-dC treatment was carried out. These two procedures confirmed that CpG island hypermethylation was the cause of the gene silencing in HCC. Over-expression of CRH-BP in HCC cell lines did not affect cell proliferation in liquid culture and anchorage- independent growth in soft agar. We thus successfully demonstrated that CRH-BP was a gene silenced in HCC due to CpG island hypermethylation and may have potential to be a diagnostic marker for HCC.