Prognostic value of Wnt inhibitory factor-1 expression in hepatocellular carcinoma that is independent of gene methylation

Abstract

Recently, Wnt inhibitory factor-1 (WIF-1) was found to be epigenetically inactivated in several solid tumors, but the biological and clinical relevance of WIF-1 methylation and expression status in hepatocellular carcinoma (HCC) are still unclear. In the present study, reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR were used to examine the WIF-1 expression and methylation in HCC cell lines. In addition, methylation and expression status of WIF-1 in 105 HCC cases were correlated with clinicopathological parameters and prognosis after tumor resection. WIF-1 was expressed in one HCC cell line and L02, both of which were not methylated in promoter region. DNA hypermethylation of WIF-1 promoter was identified in the other four HCC cell lines without WIF-1 expression. In neoplastic and non-neoplastic tissue samples, the rates of WIF-1 methylation were 61.9% and 37.1% (P = 0.001), respectively. WIF-1 was significantly downregulated in neoplastic tissues at messenger ribonucleic acid (mRNA) level, as compared to adjacent non-neoplastic tissues (P = 0.006). A significant inverse association was observed between WIF-1 methylation of and WIF-1 expression (P 0.017, R = -0.232). Methylation of WIF-1 was not associated with patient survival. In contrast, patients whose tumors exhibited negative WIF-1 mRNA expression had lower rates of overall survival. These findings suggested that aberrant methylation of WIF-1 is a common event in hepatocarcinogenesis. In addition, expression, but not methylation, of WIF-1 is a predictor of good outcome in patients undergoing resection of HCC.