The Relationship Between Aberrant Promoter Methylation Of Multiple Genes And Prognosis In Hepatocellular Carcinoma

Objective: To study the relationship between the gene promoter methylation state of DAPK,FHIT and SLIT2 genes and the clinical pronosis of patient in hepatocellular carcinoma (HCC). Methods: The technique of methylation-specific PCR (MSP) was adopted to investigate the promoter hypermethylation of DAPK,FHIT及SLIT2 genes in 50 HCCs after a curative resection. The relationship between the frequency of hypermethylation of the genes and tumor recrudescence data was analyzed. Results: In all patients with HCC, the frequency of hypermethylation in DAPK,FHIT and SLIT2 were 82.0% (41/50), 68 .0% (34/50) and 54.0% (27/50), respectively. We divided all those cases into two groups according to the follow-up neoplasm recurrence results.And in the group of one year without tumor recrudescence, the frequency of hypermethylation in DAPK,FHIT and SLIT2 were 76.9%(20/26),53.8% (14/26),50% (13/26) , respectively; in the group of less than one year with tumor recrudescence were 87.5%(21/24),83.3%(20/24),58.3%(14/24), respectively. Those three genes have higer frequency among the group of less than one year with tumor recrudescence ,The frequency hypermethylation of FHIT gene is especially higher in the group of less than one year with tumor recrudescence(p=0.036). In the group of less than one year with tumor recrudescence,there is two cases which has one or none gene hypermethylation,and there is twenty-two cases which have two or three genes hypermethylation ;and in the group of one year without tumor recrudescence,the cases are eleven and fifteen, respectively. There is a statistical prognosis difference between those cases with two or three promotors hypermethylation and those cases with none or one(p=0.006).Conclusions: The results strongly suggest that,Hypermethylation of multiple gene promotors are common events in HCC. In patients with HCC, aberrant DNA methylation is significantly associated with poor prognosis. Detection of multiple gene promotors hypermethylation in tumor tissue, especially FHIT gene, is therefore a useful index to predict the prognosis of HCC. FHIT maybe can serve as a biomarker for the prognosis, after a curative resection。...