ABSTRACT: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human malignancies and its impact on mortality is significant and well documented. Biomarkers have been developed for early HCC detection, with serum α-fetoprotein (S.AFP) being the most widely used clinically, but with relatively low diagnostic sensitivity. Therefore new biomarkers are needed for early HCC detection to improve overall-survival rates. METHODS: Blood RASSF1A promoter methylation was evaluated using methylation specific PCR in patients with chronic liver diseases together with its potential use as a biomarker for detecting HCC in comparison to or in association with S.AFP. RESULTS: Blood RASSF1A promoter methylation was detected in 70% of HCC patients on top of hepatitis C virus- associated liver cirrhosis, 28.5% of hepatitis C virus-associated liver patients and 16.6% of bilharzial liver fibrosis patients. However none of the healthy control subjects showed blood RASSF1A promoter methylation. The sensitivity, specificity, PPV and NPP of blood RASSF1A promoter methylation for HCC diagnosis were 70%, 83.3%, 73.7% and 80.6% respectively. On the other hand the sensitivity, specificity, PPV and NPP of S.AFP with a cut off value of 33.6 for HCC diagnosis were 85%, 80%, 88.9% and 90.7% respectively. Moreover it was found that the combined use of RASSF1A promoter methylation status and S.AFP is better than S.AFP use alone in HCC prediction. CONCLUSION: RASSF1A promoter methylation plays an important role in the process of human hepatocarcinogenesis and is related to hepatic inflammation due to bilharziasis and viral hepatitis. Moreover it can be considered as an important biomarker for the diagnosis of HCC when combined with S.AFP. |
