Methylation of tumour suppressor genes <i>RUNX3, RASSF1A</i> and <i>E-Cadherin</i> in HCV-related liver cirrhosis and hepatocellular carcinoma

Abstract

<b>Background</b>: HCV infection is related to aberrant methylation of several genes. <i>RASSF1A, E-Cadherin</i> and <i>RUNX3</i> are tumour suppressor genes that may be inactivated by hypermethylation in many tumours including hepatocellular carcinoma (HCC). We hypothesized that methylation is a diagnostic biomarker for HCC in patients with HCV-related liver cirrhosis.<b>Methods</b>: We recruited 207 cases of HCV-related liver cirrhosis, 193 HCC patients and 53 healthy controls. Methylation-specific polymerase chain reaction for detection of circulating hypermethylated <i>RASSF1A, E-Cadherin</i>and <i>RUNX3</i>. Alpha fetoprotein (AFP) was measured by commercial immunoassay.<b>Results</b>: Significant hypermethylation of the three genes was found in the HCC group compared to both cirrhosis and healthy groups (<i>P</i> < 0.001), whereas no significant difference in hypermethylation was found between cirrhosis and healthy groups (<i>P</i> = 0.17, 0.50 and 0.14, respectively). No significant links were found between hypermethylated <i>RASSF1A, E-Cadherin</i> and <i>RUNX3</i> and stages of Barcelona Clinic of Liver Cancer score (<i>P =</i>0.21, 0.63 and 0.98, respectively). No significant associations were found between AFP value and hypermethylated genes in cirrhosis and HCC groups (<i>P</i> = 0.82) except with <i>E-Cadherin</i> in HCC (<i>P</i> = 0.02). In multiple regression analysis, <i>RASSF1A</i> and <i>E-Cadherin</i> were predictors of HCC within cirrhosis cases, but only <i>E-Cadherin</i> was an independent risk factor for prediction of HCC in cases with low AFP (<i>P</i> = 0.01).<b>Conclusions</b>: The presence of hypermethylated serum <i>RASSF1A, E-Cadherin</i> and <i>RUNX3</i> is linked to HCC in patients with HCV-related cirrhosis. Only <i>E-Cadherin</i> is an independent risk factor for prediction of HCC with low AFP. These findings may be of diagnostic value.