Zhen Ding1, Ye-Ben Qian, Li-Xin Zhu, Qi-Ru Xiong. 1. Department of Surgery, First Affiliated Hospital of Anhui Medical University, 218 Jixi avenue, Hefei 230022, Anhui province, China.
Abstract
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 (chi(2) =7.79, P < 0.05; chi(2) = 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 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 (chi(2) =7.79, P < 0.05; chi(2) = 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.
Authors: A Durnez; C Verslype; F Nevens; J Fevery; R Aerts; J Pirenne; E Lesaffre; L Libbrecht; V Desmet; T Roskams Journal: Histopathology Date: 2006-08 Impact factor: 5.087