CAJ | 학술논문

目的探讨RAS相关区域家族1A基因(RASSF1A)甲基化对预测行肝细胞癌手术切除术后患者预后的价值.方法纳入260例行手术切除的肝细胞癌患者,留取其肝细胞癌组织和距病变外缘2 cm处的癌旁组织,并收集其临床病理资料.采用甲基化特异性PCR方法检测肝细胞癌组织和配对的癌旁组织中RASSF1A的甲基化状态.采用卡方检验分析RASSF1A甲基化的表达率及其与临床病理特征的关系.采用Log-rank检验分析RASSF1A甲基化与总生存率的关系.采用单因素和多因素Cox回归分析确定肝细胞癌预后的影响因素.结果 260份肝细胞癌组织和配对的癌旁组织中,214份(82.3％)的肝细胞癌组织中存在RASSF1A基因启动子区异常甲基化,配对的癌旁组织中有101份(38.8％)发生甲基化,差异有统计学意义(x2=102.824,P＜0.01).RASSF1A甲基化与肝细胞癌患者的年龄、性别、是否肝硬化、AFP水平、肿瘤最大径、巴塞罗那临床肝癌(BCLC)分期、是否HBV感染、是否吸烟、是否饮酒之间均无相关性(P均＞0.05).RASSF1A甲基化阴性患者的5年生存率为93％,RASSF1A甲基化阳性患者的为51％,两者的总体生存率差异有统计学意义(x2=26.556,P＜0.01).单因素和多因素Cox回归分析发现,肝硬化、BCLC分期和RASSF1A甲基化是肝细胞癌患者术后死亡的主要影响因素(Wald值分别为16.767,8.791,16.286;P均＜0.01).结论 RASSF1A甲基化不仅是肝细胞癌患者行手术切除术后生存率的预测因子之一,而且也是肝细胞癌的独立预后因素.
목적 탐토RAS상관구역가족1A기인(RASSF1A)갑기화대예측행간세포암수술절제술후환자예후적개치.방법 납입260례행수술절제적간세포암환자,류취기간세포암조직화거병변외연2 cm처적암방조직,병수집기림상병리자료.채용갑기화특이성PCR방법검측간세포암조직화배대적암방조직중RASSF1A적갑기화상태.채용잡방검험분석RASSF1A갑기화적표체솔급기여림상병리특정적관계.채용Log-rank검험분석RASSF1A갑기화여총생존솔적관계.채용단인소화다인소Cox회귀분석학정간세포암예후적영향인소.결과 260빈간세포암조직화배대적암방조직중,214빈(82.3％)적간세포암조직중존재RASSF1A기인계동자구이상갑기화,배대적암방조직중유101빈(38.8％)발생갑기화,차이유통계학의의(x2=102.824,P＜0.01).RASSF1A갑기화여간세포암환자적년령、성별、시부간경화、AFP수평、종류최대경、파새라나림상간암(BCLC)분기、시부HBV감염、시부흡연、시부음주지간균무상관성(P균＞0.05).RASSF1A갑기화음성환자적5년생존솔위93％,RASSF1A갑기화양성환자적위51％,량자적총체생존솔차이유통계학의의(x2=26.556,P＜0.01).단인소화다인소Cox회귀분석발현,간경화、BCLC분기화RASSF1A갑기화시간세포암환자술후사망적주요영향인소(Wald치분별위16.767,8.791,16.286;P균＜0.01).결론 RASSF1A갑기화불부시간세포암환자행수술절제술후생존솔적예측인자지일,이차야시간세포암적독립예후인소.
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.