Promoter Methylation And MRNA Expression Of SFRP1 And APC Gene In Hepatocellular Carcinoma

Objective To investigate the promoter methylation status and mRNA expression of SFRP1 and APC gene in hepatocellular carcinoma.Methods Methylation status of APC and SFRP1 gene promoter were detected by methylation specific PCR in 30 hepatocellular carcinomas and adjacent non-cancerous tissues,10 normal liver tissue as control.Expression of SFRP1 and APC mRNA was also determined by reverse transcriptase PCR in the three tissues.The relationship between methylation and clinical data,mRNA expression and clinical data, methylation and mRNA expression of the tow genes were analyzed.Results SFRP1 promoter methylation was observed in 11/30,4/30,0/10 and APC promoter methylation was observed in 14/30,5/30 and 0/10 in hepatocellular carcinomas,adjacent non-cancerous tissues and normal control tissues, respectively.Methylation of SFRP1 and APC genes in hepatocellular carcinoma increased significantly compared with adjacent non-cancerous tissues and normal control tissues(x~2=4.356,P=0.037;x~2=6.239,P=0.012) and there was no significant difference in methylation between normal control tissues and adjacent non-cancerous tissues.No associations were found between methylation status of SFRP1 gene and clinical data.Significant differences of the APC promoter methylation were observed in ages and in tumors with or without pseudo-capsule in HCC tissues.Methylation of APC gene was significant frequency in younger(＜60 years) than in older(≥60 years)(P=0.045).It was significant frequency in tumors with pseudo-capsule than in tumors without pseudo-capsule (P=0.025 ).Significant differences of the APC promoter methylation were also observed in tumor number and in tumors with or without pseudo-capsule in adjacent non-cancerous tissues.Methylation of APC in multiple tumor's adjacent non-cancerous tissues were more frequency than which in solitary tumor's(P = 0.006 ).It was more frequency in non-cancerous tissues of tumor with pseudo-capsule than which in tumor without pseudo-capsule(P = 0.019).HCC recurrence rate in one year in patients with SFRP1 or APC methylation in HCC tissue was equivalency compared with whom without SFRP1 or APC methylation in HCC tissue in one year.Average expression of SFRP1 mRNA was 0.23,0.30 and 0.32 in hepatocellular carcinomas,adjacent non-cancerous tissues and normal control tissues,respectively.The average expression in hepatocellular carcinomas were less than adjacent non-cancerous tissues and normal control tissues significantly(P＜0.05),but there was no significant difference between adjacent non-cancerous tissues and normal control tissues(P = 0.48).There was no correlation between expression of SFRP1 gene and clinical data.There was no difference in average expression of SFRP1 mRNA between methylation and unrnethylation in hepatocellular carcinomas(P = 0.10).Average expression of APC mRNA was 0.76,0.86 and 0.84 in the aforesaid three tissues respectively, there was no significant difference among them.Significant differences of the APC mRNA expression were observed between tumors with pseudo-capsule and without pseudo-capsule.Significant differences were also observed in different tumor patho-classed.Expression of APC mRNA were more significantly in tumors with pseudo-capsule than which in tumors without pseudo-capsule and APC mRNA expression were more significantly in tumors which wasⅠ～Ⅱpatho-classed than which wasⅢpatho-classed in HCC tissues.There was no difference in average expression of APC mRNA between methylation and unmethylation in hepatocellular carcinomas(P = 0.32 ).There was no correlation in methylation between SFRP1 gene and APC gene and also no correlation in expression between SFRP1 mRNA and APC mRNA in hepatocellular carcinomas and in adjacent non-cancerous tissues.Conclusion The aberrant promoter methylation of APC and SFRP1 genes are both related to hepatocarcinogenesis and progress.Methylation of APC gene probably has effect on the invasion and metabasis of hepatocellular carcinoma.The relationships between methylation and mRNA expression of the two genes are remain unclear in hepatocellular carcinomas tissues.