Circulating hypermethylated RASSF1A as a possible marker of hepatocellular carcinoma in chronic hepatitis C patients

Abstract Background Hepatocellular carcinoma (HCC) is a worldwide health issue and the third most common cause of cancer-related fatalities globally. The Ras association domain family 1 isoform (RASSF1A) is a tumor suppressor gene; it plays a role in maintaining microtubule stability, cell cycle progression, and induction of apoptosis. The carcinogenic impact of methylation, an important epigenetic alteration, is well recognized in HCC. Therefore, we aimed to evaluate the significance of plasma concentration of methylated RASSF1A in patients with post-hepatitis C virus (HCV) cirrhosis as a non-invasive diagnostic indicator for HCC. Methods The levels of methylated RASSF1A were measured in the plasma of 120 individuals divided into three groups (40 individuals each): HCC patients with chronic HCV infection, cirrhotic patients after hepatitis C without HCC, and a healthy control group matched for age and sex. Methylation-sensitive restriction enzyme digestion and real-time quantitative polymerase chain reaction techniques were used to assess the RASSF1A expression levels. Results patients with HCC showed markedly elevated levels of circulating hypermethylated RASSF1A compared to post-hepatitis C patients and control groups. Moreover, a statistically significant association between RASSF1A and various clinico-pathological parameters was noted. The plotted receiver operating characteristic (ROC) curves indicated that plasma RASSF1A significantly differentiated between HCC and cirrhotic patients. Conclusion Circulating hypermethylated RASSF1A may serve as a non-invasive diagnostic marker to differentiate HCC in post-HCV cirrhotic patients and to assess their progression.