DKK-1、DKK-2和GPC3蛋白在肝细胞癌组织中的表达及其临床意义  

Expressions of DKK-1,DKK-2 and GPC3 proteins in hepatocellular carcinoma and their clinical significance

作　　者：赵衡[1] 葛超[1] 李红[1] 李锦军[1] 

机构地区：[1]上海交通大学肿瘤研究所癌基因及相关基因国家重点实验室,上海200032

出　　处：《肿瘤》2010年第5期428-432,共5页Tumor

基　　金：国家自然科学基金资助项目(编号:NSFC/RGC30731160004);国家重点基础研究发展计划(973计划)课题(编号:2009CB521803)

摘　　要：目的:探讨DKK-1、DKK-2和人磷脂酰肌醇蛋白聚糖3(glypican3,GPC3)蛋白在肝细胞癌组织中的表达及临床意义。方法:采用组织芯片联合免疫组织化学法检测DKK-1、DKK-2和GPC3蛋白在10例正常肝、12例肝硬化、57例肝细胞癌及癌旁肝组织中的表达差异,并分析其临床意义。结果:免疫组织化学检测结果发现,DKK-1和DKK-2在肝细胞癌组织中阳性染色率分别为59.65%(34/57)和57.89%(33/57);GPC3只在肝细胞癌组织中表达,其阳性染色率为47.37%(27/57),而在正常肝、肝硬化及癌旁肝组织中均呈阴性表达。DKK-1与DKK-2阳性表达之间存在密切相关性(χ2=0.570,P=0.000),DKK-2与GPC3阳性染色之间也存在相关性(χ2=0.272,P=0.041)。统计分析DKK-1、DKK-2及GPC3在肝细胞癌组织中阳性染色与肝癌患者性别、年龄、血清甲胎蛋白(α-fetoprotein,AFP)水平、乙肝表面抗原(hepatitis B surface antigen,HBsAg)、肿瘤大小、病理学分级、静脉浸润以及是否伴随肝硬化等的相关性,结果表明血清AFP水平与GPC3表达呈正相关(P=0.007),HBsAg与DKK-1表达呈正相关(P=0.037),DKK-1阳性染色与肝细胞癌组织分级存在相关性(P=0.014),与其他参数则无相关性。结论:GPC3在肝细胞癌组织的阳性染色率为47.37%,GPC3染色阴性的肝细胞癌组织中DKK-1和DKK-2双阳性染色率为40.00%,而GPC3(+)联合DKK-1(+)/DKK-2(+)/GPC3(-)可将肝细胞癌的免疫组织化学检出率提高至68.42%(39/57),降低肝癌免疫组织化学检测中的假阴性率。Objective：To explore the different expression and significance of human Dickkipf（DKK）-1,DKK-2 and glypican 3（GPC3） in hepatocellular carcinoma（HCC） tissues.Methods：Combined tissue microarray and immunohistochemical staining（IHC） were performed to detect the differential expressions of DKK-1,DKK-2 and GPC3 proteins in 10 human normal liver tissues,12 cirrhotic liver tissues,57 non-cancerous liver tissues as well as matched primary HCC tissues.Its clinical pathological significance was statistically analyzed by SPSS 16.0 software.Results：IHC positive rates of DKK-1 and DKK-2 were 59.65%（34/57） and 57.89%（33/57）,respectively.However,GPC3 positive immunostaining was only observed in HCC tissues,with expression rate of 47.37%（27/57）,and GPC3 negative staining was found in normal liver,cirrhotic liver and non-cancerous liver tissues.There was a good correlation of positive rates of DKK-1 with that of DKK-2（χ^2=0.570,P=0.000）,or between DKK-2 and GPC3（χ^2=0.272,P=0.041）.Statistic analysis showed that positive immunostaining of DKK-1,DKK-2 and GPC3 protein had no association with gender,age,vein invasion and cirrhosis of HCC patients（P0.05）;but there existed correlation between GPC3 staining and serum AFP levels（P=0.007）,between DKK-1 staining and serum HBsAg levels（P=0.037）,as well as between DKK-1 and pathological grades（P=0.014） of HCC patients.Conclusion：Positive immunostaining rate of GPC3 protein in HCC was 47.37%,and in GPC3-negative HCC samples,DKK-1/DKK-2 double positive staining rate was 40.00%.When combining GPC3（＋） with DKK-1（＋）/DKK-2（＋）/GPC3（-）,the positive diagnostic rate of HCC was 68.42 %（39/57）,which remarkably decreased the false-negative rate in IHC examination of HCC.

关 键 词：癌 肝细胞 免疫组织化学 硫酸乙酰肝素蛋白聚糖 蛋白质阵列分析 DKK Glypican3 

分 类 号：R735.7[医药卫生—肿瘤]