DNA hypermethylation of zygote arrest 1 (ZAR1) in hepatitis C virus positive related hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world, and its prognosis is generally poor. Epigenetic alteration such as DNA methylation has been shown to be important in the development of human cancers including HCC. Here, we analyzed the methylation status of ZAR1, which has been reported to be aberrantly methylated in a few human cancers. METHODS: We investigated the methylation status of ZAR1 in 88 HCV-positive HCC and matched nontumorous liver tissue samples and 4 normal liver tissue samples used as a control using MassARRAY EpiTYPER. Further statistical analysis was performed to determine the relationship between methylation level and patient clinicopathological features and prognosis. RESULTS: CpG islands in ZAR1 exon 1 showed a higher methylation level in all 88 HCC than in nontumorous tissues. The hypermethylation group, whose cancer tissues showed a twofold or higher methylation level compared with nontumorous tissues, showed a significantly higher serum AFP (p = 0.018) and lower serum albumin (p = 0.001) and single rather than multiple tumors (p = 0.031) compared with the hypomethylation group. Multivariate regression analyses were performed to identify which of the following factors were the predictors of the hypermethylation group: serum albumin, AFP, and tumor multiplicity. This study showed that patients who had Zar1 hypermethylation in the HCC tissues had a significantly lower serum albumin level than those in the hypomethylation group (p = 0.007). CONCLUSION: Although it is still unknown how ZAR1 hypermethylation affects HCC development, it could be a potential marker to detect HCV-related HCC.