Glypican-3在原发性肝细胞癌中的表达及其对预后的影响  

Expression of glypican-3 in hepatocellular carcinoma and its clinical significance

作　　者：付顺军[1] 李绍强[1] 林杰[1] 彭宝岗[1] 梁力建[1] 

机构地区：[1]中山大学附属第一医院肝胆外科,广东广州510080

出　　处：《中国病理生理杂志》2010年第12期2351-2357,共7页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金资助项目(No.07001626);广东省科技计划资助项目(No.2009B030801124);广东省医学科学基金资助项目(No.A2007172)

摘　　要：目的:探讨磷脂酰肌醇蛋白聚糖-3(GPC3)在原发性肝细胞癌(HCC)中的表达及其临床意义。方法:采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法检测了59例HCC组织及其癌旁组织、10例肝内胆管细胞癌组织、11例肝硬化肝组织、14例正常肝组织(肝血管瘤旁)中GPC3的表达。应用Kap lan-M e ier法进行生存分析;Cox比例风险回归模型进行患者术后无瘤生存的独立危险因素分析。结果:GPC3 mRNA在HCC组织中的阳性率为83.1%(49/59),明显高于癌旁组织的35.6%(21/59)(2=27.53,P<0.01)。GPC3蛋白在HCC中的阳性率为78.0%(46/59),也明显高于在癌旁组织的阳性率32.2%(19/59)(2=24.97,P<0.01)。而GPC3在肝内胆管细胞癌(ICC)、肝硬化和正常肝组织中不表达。Kap lan-M e ier生存分析显示在HCC组织中GPC3(+)组病人的1年无瘤生存率明显低于GPC3(-)组(33.6%vs72.7%,P<0.05);癌旁组织GPC3(+)组病人的1年无瘤生存率也低于GPC3(-)组(23.5%vs40.1%,P<0.05);随着GPC3在HCC组织中表达强度的增加,患者的无瘤生存率也明显降低。Cox风险回归模型分析结果显示,肿瘤AFP阳性[优势比(OR)]=0.372,95%置信区间(CI):0.140-0.900,P<0.05]、肿瘤大小(OR=5.215,95%C:I 1.737-15.656,P<0.01)、癌旁组织GPC3表达(OR=0.226,95%CI:0.085-0.599,P<0.01)、肿瘤GPC3表达的强度(OR=1.946,95%C:I 1.080-3.507,P<0.05)是影响患者术后无瘤生存率的独立危险因素。结论:GPC3在肝细胞癌组织中高表达,而在肝内胆管细胞癌组织、肝硬化组织和正常肝组织不表达。癌旁组织GPC3表达、肿瘤GPC3表达的强度是影响HCC患者术后无瘤生存率的独立危险因素;但对患者1年总体生存率无明显影响。AIM：To study the expression of glypican-3 in hepatocellular carcinoma（HCC） tissues and to clarify its clinical significance.METHODS： The expression of GPC3 was detected in 59 cases of HCC and their para-cancerous tissues,10 cases of intrahepatic cholangiocellular carcinoma（ICC）,11 cases of cirrhotic tissues and 14 cases of normal liver tissues（around haemangioma） by RT-PCR and immunohistochemical staining.The survival curves were constructed using Kaplan-Meier method and evaluated using the log-rank test.In addition,the Cox proportional hazards regression model was established to identify the factors that were independently associated with disease-free survival（DFS）.RESULTS： The mRNA expression of GPC3 in the HCC tissues was significantly higher than that in the para-cancerous tissues（83.1% vs 35.6%,2=27.53,P0.01）.The protein expression of GPC3 in the HCC tissue was also higher than that in the para-cancerous tissues（78.0% vs 33.2%,2=24.97,P0.01）.The expression of GPC3 in ICC tissues,liver cirrhosis tissues and normal liver tissues was undetectable.Kaplan-Meier survival analysis indicated that the GPC3（＋）HCC patients had worse 1-year DFS than that of GPC3（-） patients（33.6% vs 72.7%,P0.05）.The HCC patients with para-cancerous GPC3（＋） also had worse 1-year DFS than that of the para-cancerous GPC3（-） patients（23.5% vs 40.1%,P0.05）.The DFS rate decreased significantly as the expression intensity of GPC3 increased.The Cox regression model analysis indicated that AFP（＋）（odd ratio=0.372,95% confidence interval： 0.140-0.900,P0.05）,tumor size（odd ratio=5.215,95% confidence interval： 1.737-15.656,P0.01）,para-cancerous tissue GPC3（＋）（odd ratio=0.226,95% confidence interval： 0.085-0.599,P0.01） and the intensity of GPC3 expression in HCC tissue（odd ratio=1.946,95% confidence interval： 1.080-3.507,P0.05） were the independent risk factors linked to DFS of patients.CONCLUSION： GPC3 protein is highly expressed in the HCC tissues,

关 键 词：磷脂酰肌醇蛋白聚糖-3 癌 肝细胞 预后 

分 类 号：R735.7[医药卫生—肿瘤]