Study On The Promoter Hypermethylation Of RASSF1A In Hepatocellular Carcinoma

Objective to investigate the relationship between the promoter methylation of RASSF1A and expression of RASSF1A proteins and tumorigenesis and development in hepatocellular carcinoma,and The significance and value of the promoter methylation of RASSF1A as a new tumor molecule marker in early diagnosis or no wound diagnosis of HCC.Methods to detect the promoter methylation of RASSFIA status of Ras association domain family IA(RASSFIA)in the tumor tissues and adjacent noncancerous tissues and serums of 35 HCC patients,5 normal hepatic tissues and 10 normal control serums by methylation-specific PCR(MSP),meanwhile detect the RASSFIA proteins in 98 tumor tissues and adjacent noncancerous tissues by tissue arrays.Results(1)RASSFIA promoter methylation was detected in 31 of the 35 HCC tissues(88.6%),and the exhaustive methylation samples were 18 among the 31 tissues,the part methylation was 13;RASSFIA promoter methylation was detected in 18 of the 35 adjacent noncancerous tissues of live cirrhosis or chronic hepatitis(51.4%),and the exhaustive methylation samples were 11 among the 31 tissues,the part methylations was 7.The RASSFIA methylation-positive rate was significantly higher in the tumor tissues than in adjacent noncancerous tissues of live cirrhosis or chronic hepatitis(88.6% vs 51.4%,P＜0.05).No RASSFIA methylation was detected in 5 normal hepatic tissues.Of the paired serum from the 35 HCC patients,aberrant methylation was detected in 14(40%),no RASSFIA methylation was detected in 10 normal control serums.The association of RASSFIA methylation in tumor tissues and adjacent noncancerous tissues of HCC patients with clinicopathological characteristics such as sex,cirrhosis,HBV,AFP,tumor size,capsular,portal vein tumor embolus or patho-grade was analyzed,it was not found statistic association between them.The statistic association was not found between the RASSFIA methylation in the paired serum from the 35 HCC patients with corresponding clinicopathological characteristics. (2)Succeed to prepare 2 dry pieces of tissue arrays.Total effective rate of arrays was 97.4%(191/196),and the group of tumor tissues was 98.0%(96/98),the group of adjacent noncancerous tissues was 96.9%(95/98).The positive rate of the expression of RASSFIA proteins in HCC tissues was 39.58%(38/96),significantly lower that in adjacent noncancerous tissues 67.37%(64/95,P＜0.05).The expression of RASSF1A proteins was associated with HCC patients' age,AFP,portal vein tumor embolus,capsular infiltration or tumor nodes number:the expression of RASSF1A proteins was not associated with HCC patients' sex,cirrhosis,histological classification or tumor size.Conclusions The promoter methylation of RASSF1A and expression of RASSF1A proteins may play an important role in the tumorigenesis and development of HCC,The promoter methylation of RASSF1A may be a new tumor molecule marker of HCC,the detection of RASSF1A methylation may have some significance and value in early diagnosis or no wound diagnosis of HCC.