Prognostic value of RAS association domain family 1A gene methylation in patients with hepatocellular carcinoma after surgery

Abstract

Objective To evaluate the prognostic value of RAS association domain family 1A gene (RASSF1A) methylation in patients after hepatocellular carcinoma (HCC) hepatectomy.Methods A total of 260 patients with HCC who underwent hepatectomy were enrolled.HCC tissues and tumor adjacent tissues which were 2 cm away from the tumor edge of the patients were obtained.The clinicopathological data of patients were collected.The methylation of RASSF1A in HCC tissues and corresponding tumor adjacent tissues was determined by methylation specific polymerase chain reaction (PCR).The correlation between the expression rate of RASSF1A methylation and clinicopathological characteristics was analyzed by chi-square test.Log-rank test was performed to analyze the relation between RASSF1A methylation and overall survival rate.Univariate and multivariate Cox statistical techniques were used to identify the influence factors in the prognosis of HCC.Results Among 260 HCC tissues and corresponding tumor adjacent tissues,RASSF1A promoter hypermethylation was detected in 214 HCC tissues (82.3 ％) and 101 corresponding tumor adjacent tissues (38.8％),and the difference was statistically significant (x2 =102.824,P ＜ 0.01).There was no correlation between RASSF1A methylation and age,gender,liver cirrhosis,α-fetoprotein level,maximum diameter of tumor,Barcelona Clinic Liver Cancer (BCLC) stage,hepatitis B virus (HBV) infection,smoking and alcohol drinking (all P＞0.05).The 5-year overall survival rate of patients with negative RASSF1A methylation was 93％,while that of patients with positive RASSF1A methylation was 51 ％,and the difference in overall survival rate between the two groups was statistically significant (x2 =26.556,P ＜ 0.01).Univariate and multivariate Cox regression analysis indicated that liver cirrhosis,BCLC stage and RASSF1A methylation were the main influence factors in the death of patients with HCC after surgery (Wald=16.767,8.791,16.286; all P＜0.01).Conclusion RASSF1A methylation is not only one of the predictive factors of survival rate in patients with HCC after hepatectomy,but also an independent prognostic factor of HCC. Key words: Carcinoma hepatocellular; RASSF1A gene; Methylation; Prognosis