AIM:To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma(HCC).METHODS:DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors,but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC.Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction(PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control.The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR.The relationship between methylation,mRNA expression,and clinical data,as well as methylation and mRNA expression of the two genes were analyzed.RESULTS:The methylation of DKK-3 and WIF-1 genes in HCC increased significantly compared with adjacent non-cancerous tissues and normal control tissues(χ2 =7.79,P < 0.05;χ2 = 4.89,P < 0.05),and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed.In HCC tissues,significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis,and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis.The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly compared with normal control tissues.The average expression of WIF-1 mRNA showed no significant difference among the three tissues.The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased.CONCLUSION:The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC,and may be a far-reaching significance in early diagnosis and therapy of HCC. AIM: To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma (HCC). METHODS: DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors, but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC. Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction (PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control. The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR. The relationship between methylation, mRNA expression, and clinical data, as well as methylation Results of the methylation of DKK-3 and WIF-1 genes in HCC increased significantly with adjacent non-cancerous tissues and normal control tissues (χ2 = 7.79, P <0 .05; χ2 = 4.89, P <0.05), and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed. Significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis , and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis. The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly with normal control tissues. The average expression of WIF-1 mRNA showed no significant difference among the three tissues. The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased. CONCLUSION: The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC, and may be a far-reaching significance in early diagnosis and therapy of HCC.