Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C?

Background and study aimsThe detection of the promoter hypermethylation of RASSF1A in serum DNA could be a valuable biomarker for early detection of preneoplastic lesions and early cancer development among high-risk populations who are at a high risk of hepatocellular carcinoma (HCC). Therefore, we aimed determining the serum level of methylated RASSF1A sequence in patients with chronic hepatitis C viral infection and to evaluate the predictive value of it as a diagnostic marker for HCC in patients with chronic hepatitis C viral infection.Patients and methodsSerum levels of methylated RASSF1A were detected and measured using real-time PCR after digestion with a methylation-sensitive restriction enzyme in 40 patients with chronic HCV infection, 40 patients with HCC (on top of HCV) and 20 controls.ResultsMethylated RASSF1A was detected in 10% of the controls, 62.5% of HCV group and in 90% of HCC group. Chronic HCV patients had insignificantly higher levels than the controls. The levels were significantly higher in patients with HCC compared to the controls (p = 0.0001) and chronic HCV patients (p = 0.001). By logistic regression analysis, the serum methylated RASSF1A was found to differentiate HCC patients from healthy controls with an AUROC of 0.83 nmol/L, and an overall predictive accuracy of 77.5%. It was able to differentiate patients with HCC from those with chronic HCV infection alone with an AUROC of 0.733 and an overall predictive accuracy of 72.5%.ConclusionThe mean serum levels of methylated RASSF1A could be of value for early diagnosis of HCC especially in high risk patients with HCV infection.