Relationship between promoter methylation and mRNA expression of RUNX3 gene in human primary hepatocellular carcinoma and its significance

Objective To determine the promoter methylation and mRNA expression of human runt-related transcription factor 3 (RUNX3) gene in hepatocellular carcinoma (HCC) and the relationship between the methylation and clinicopathological features.Methods The methylation status of 10 samples from human normal liver tissues,75 samples from HCC and adjacent normal tissues,and its relationship with clinicopathological features were analyzed by methylation-specific polymerase chain reaction (MSP).The expression of RUNX3 mRNA in all samples was detected.Results MSP results revealed that abnormal CpG island methylation of RUNX3 gene was found in 34 cases of HCC (45.3％ ),7 cases (9.3％ ) of adjacent normal tissues,and no abnormal CpG island methylation of RUNX3 was found in normal liver tissues (x2 =29.18,P ＜0.01 ).The down-regulation of RUNX3 mRNA was found in 45 out of 75 cases of HCC.Twenty-severn out of 45 (60％) HCC cases with lower expression of RUNX3 gene had the promoter hypermethylation.Statistically significant links were found between low RUNX3 mRNA levels and abnormal promoter methylation (x2 =9.77,P ＜0.01 ).The level of RUNX3 mRNA in HCC without methylation was over 4-fold higher than that in HCC with methylation.RUNX3 gene CpG island methylation was significantly correlated with cirrhosis (x2 =5.07,P ＜ 0.05 ).Conclusion Promoter hypermethylation is an important mechanism for low expression of RUNX3 in HCC and is closely correlated to cirrhosis. Key words: RUNX3 ; Carcinoma,hepatocellular; Methylation