癌胚型GPC-3特异诊断原发性肝细胞癌及其靶向治疗进展  

Oncofetal glypican-3: Specific diagnosis and targetedtherapy for primary liver cancer

作　　者：潘刘翃 姚敏[2] 王理[3] 姚登福[1] 

机构地区：[1]南通大学附属医院临床医学研究中心,江苏省南通市226001 [2]南通大学医学院免疫学教研室,江苏省南通市226001 [3]南通大学医学院医学信息学教研室,江苏省南通市226001

出　　处：《世界华人消化杂志》2015年第9期1379-1386,共8页World Chinese Journal of Digestology

基　　金：国家国际科技合作专项基金资助项目;No.2013DFA32150;江苏省"六大人才高峰"基金资助项目;Nos.2014-YY-028;2013-WSW-011;江苏省高校优秀青年教师青蓝工程基金资助项目;No.2014-NTU-YM~~

摘　　要：原发性肝细胞性肝癌(primary hepatocellular cancer,PHC)的发生、发展是一个多因素、多步骤、多中心的复杂过程,他的早期诊断和有效治疗至关重要.磷脂酰肌醇蛋白多糖-3(glypican-3,GPC-3)在PHC进展过程中起重要作用.在肝细胞恶性转化过程中G P C-3呈进行性升高表达;人肝癌G P C-3阳性率与乙型肝炎表面抗原(hepatitis B surface antigen,Hbs Ag)、TNM分期、门脉癌栓及肝外转移显著相关.GPC-3及m RNA与甲胎蛋白(alpha fetoprotein,AFP)联合检测,对PHC诊断阳性率可提高至94.3%;沉默GPC-3可改变肝癌细胞迁移、转移和侵袭的生物学行为,伴随β-catenin、p-糖原合成激酶3β(pglycogen synthase kinase 3β,p-GSK3β)和cyclin D1表达明显减少,提示癌胚性GPC-3不仅是PHC特异诊断标志物,而且有可能成为PHC治疗的潜在靶点.The development and progression of primary hepatocellular cancer（PHC） are a multifactorial,multi-step,and multi-center complex process.Its early diagnosis and effective treatments are of the most importance.Glypican-3（GPC-3） plays a crucial role in PHC progression.Increased GPC-3 expression has been found during hepatocyte malignant transformation.GPC-3 levels in PHC patients are related to HBV infection,TNM stage,periportal cancerous embolus,and extrahepatic metastasis.Circulating GPC-3 or GPC-3 mRNA with AFP enhances the positive rate up to 94.3%for PHC diagnosis.Downregulating GPC-3 by specific siRNA could alter liver cancer cell biological behaviors such as migration,metastasis,and invasion;and inhibit nude mouse xenograft growth with decreased p-catenin,p-GSK3 p,and cyclin D1 expression,suggesting that oncofetal GPC-3is not only a specific diagnostic biomarker for PHC,but also a promising target for PHC therapy.

关 键 词：原发性肝细胞性肝癌 磷脂酰肌醇蛋白多糖-3 诊断 靶向治疗 

分 类 号：R735.7[医药卫生—肿瘤]