阿帕替尼靶向治疗联合TACE对晚期原发性肝癌患者的疗效及外周血RASSF1A基因甲基化的影响  

Efficacy of targeted therapy combined with TACE in the treatment of patients with advanced primary liver cancer and its effects on peripheral blood RASSF1A gene methylation

作　　者：唐路遥 付卫争 于瀚卿 TANG Luyao;FU Weizheng;YU Hanqing(Department of Oncology,Suzhou Hospital Affiliated to Anhui Medical University&Suzhou Municipal Hospital,Suzhou 234000,Anhui,China;Department of Oncology,First Affiliated Hospital of Anhui Medical University,Suzhou 234000,Anhui,China)

机构地区：[1]安徽医科大学附属宿州医院&宿州市立医院肿瘤科,安徽宿州234000 [2]安徽医科大学第一附属医院肿瘤科,安徽宿州230000

出　　处：《贵州医科大学学报》2024年第6期894-900,共7页Journal of Guizhou Medical University

基　　金：2020年度安徽高校自然科学研究项目(KJ2020A0174)。

摘　　要：目的分析阿帕替尼靶向治疗联合肝动脉化疗栓塞术(TACE)治疗晚期原发性肝癌患者疗效及对外周血Ras相关区域家族1A(RASSF1A)基因甲基化的影响。方法64例晚期肝细胞癌(HCC)患者分为单一组(n=32)与联合组(n=32),单一组行TACE治疗,联合组行阿帕替尼靶向治疗联合TACE治疗,两组患者均行标准疗程TACE治疗,于治疗1个月(1 mo)及3个月(3 mo)评估临床疗效,比较治疗前后肝功能[白蛋白(ALB)、总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)]、血清标志物[甲胎蛋白(AFP)、血管内皮生长因子(VEGF)、半胱氨酰天冬氨酸蛋白酶8(Caspase-8)]、外周血RASSF1A基因甲基化、不良反应及TACE抵抗发生率。结果单一组治疗3 mo时的客观缓解率(ORR)较治疗1 mo时下降(P<0.05),且低于联合组(P<0.05);两组患者治疗3 mo时的ALT、AST均较治疗前下降(P<0.05),且联合组低于单一组(P<0.05),两组患者治疗3 mo时的AFP均较治疗前显著降低(P<0.05);联合组治疗3 mo时的VEGF较治疗前降低(P<0.05)、Caspase-8较治疗前升高(P<0.05),联合组治疗3 mo时AFP、VEGF低于单一组(P<0.05),Caspase-8高于单一组(P<0.05);联合组治疗3 mo时RASSF1A基因甲基化阳性率明显低于治疗前(P<0.05),而单一组组内比较差异无统计学意义(P>0.05);联合组手足综合征、高血压发生率高于单一组(P<0.05),TACE抵抗发生率略低于单一组、但差异无统计学意义(P>0.05)。结论阿帕替尼靶向治疗联合TACE对晚期HCC效果及安全性良好,且对减少RASSF1A基因甲基化有利。Objective To analyze the efficacy of apatinib targeted therapy combined with transhepatic arterial chemotherapy and embolization(TACE)in the treatment of patients with advanced primary liver cancer and the effects on Ras association domain family 1A(RASSF1A)gene methylation of peripheral blood.Methods A total of 64 patients with advanced hepatic cell carcinoma(HCC)were selected as research subjects,and were randomly divided into the single group(n=32)and combined group(n=32).The single group received TACE therapy,and the combined group was given apatinib targeted therapy combined with TACE therapy.Both groups received standard course of TACE therapy,and 3 months of treatment was taken as the observation endpoint.The clinical efficacy in the two groups was evaluated,and the liver function[albumin(ALB),total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST)],serum markers[alpha-fetoprotein(AFP),vascular endothelial growth factor(VEGF),cysteinyl aspartate protease 8(caspase-8)]and peripheral blood RASSF1A gene methylation were compared before and after treatment,and the treatment-related adverse reactions were recorded.The incidence rates of TACE resistance in the two groups was evaluated by continuous follow-up observation.Results The objective response rate(ORR)after 3 mo of treatment in the single group decreased compared with that after 1 mo of treatment(P<0.05),and was lower than that in combined group(P<0.05).After 3 mo of treatment,the levels of ALT and AST in both groups decreased compared with before treatment(P<0.05),and the levels were lower in the combined group than those in the single group(P<0.05);the level of AFP was significantly declined in both groups compared with that before treatment(P<0.05),and the VEGF level in the combined group was reduced(P<0.05)while the caspase-8 level was enhanced compared with that before treatment(P<0.05),and the levels of AFP and VEGF in the combined group after 3 mo of treatment were lower than those in the single group(P<0.05)while the l

关 键 词：肝细胞癌 晚期 靶向治疗 阿帕替尼 肝动脉化疗栓塞术 RASSF1A基因甲基化 

分 类 号：R735.7[医药卫生—肿瘤]