比较基因组杂交芯片技术对肝癌组织中骨桥蛋白不同表达肿瘤细胞基因组的研究  

High-resolution analysis of genomic profiles of hepatocellular carcinoma cells with different osteopontin expression

作　　者：武金才[1] 孙冰生[1] 刘道永[1] 李国才[1] 史炯[1] 任宁[1] 叶青海[1] 钦伦秀[1] 

机构地区：[1]复旦大学肝癌研究所,复旦大学附属中山医院,复旦大学生物医学研究院癌症研究中心,上海200032

出　　处：《中华肝胆外科杂志》2008年第12期854-857,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：基金项目：国家863计划（编号：2006AA022473）;国家杰出青年基金（编号：30325041）;国家自然科学基金资助项目（编号：30600589,30371378,30430720）

摘　　要：目的探讨肝癌组织中骨桥蛋白（osteopontin，OPN）不同表达肿瘤细胞基因组的差异及其表达与临床病理特征的关系。方法免疫组化染色分析7l例肝细胞肝癌（hepatocellular carcinoma，HCC）的OPN表达，激光捕获显微切割和比较基因组杂交芯片分析肝癌中不同OPN表达肿瘤细胞基因组的改变。结果71例HCC中，OPN阳性表达29例（42．9％），表现为不均匀分布，阳性表达多位于癌巢周边、特别近肿瘤血管处，亦可见小癌结节呈广泛颗粒状表达，另有14例（19．7％）癌巢外的肝硬化组织呈OPN阳性染色；OPN过表达与肿瘤分化、脉管侵犯、肝内转移有关；OPN阳性与OPN阴性肿瘤细胞基因组相比有4q13．1q13．3、4q21．23—22．1、13q32．1-q32．3等拷贝数增加，其中阳性细胞中肿瘤相关基因如SMR3B、MUC7、EPHA5、SPP1（OPN）、CLDNIO等拷贝数明显增加。结论OPN提高肝癌细胞侵袭性而促进转移，可能与肿瘤细胞增殖、肝硬化的恶性转化有关。OPN阳性、阴性表达的肿瘤细胞之间存在肿瘤异质性。Objective To characterize intratumor genomic profiles between OPN-positive and OPN-negative HCC cancer cells and evaluate the relationship between OPN expression and clinicopathological features. Methods OPN expression was examined immunobistochemically in 71 cases of HCC. The eytogenetic changes were analyzed by array-CGH between microdiessected OPN-positive and -negative fresh HCC tissues. Results Out of the 71 HCC samples, 29 （42.9%） showed positive staining for OPN. Dispersed OPN-positive cancer cells were localized in the periphery of caneer nod- ules adjacent to stromal cells, especially in the area with a high density of vasculature. In some cases, extensively granular staining of OPN was observed in cancer nodules. Fourteen samples （19.70//oo） showed OPN immunoreactivity in cirrhotic parenchyma cells. OPN expression was significantly related to histologic grade, intrahepatic spread and vascular or bile duct invasion in HCC. Compared to OPN negative cancer cells, the OPN-positive cancer cells showed much more regions of copy number alteration with amplified 4q13.1-q13.3, 4q21.23-22.1, 13q32.1-q32.3. Some candidate tumor related genes （SMR3B, MUC7, EPHA5, SPP1, CLDN10） were detected with over 1.5-fold amplification. Conclusions OPN increases invasive ability and promotes metastatic potential of HCC cells and might mediate tumor cell proliferation and conversion to the malignant phenotype in cirrhotic parenchyma cells. Intratumor genomic heterogeneity is found between OPN-positive and-negative cancer cells.

关 键 词：癌 肝细胞 骨桥蛋白 免疫组织化学 比较基因组杂交芯片 肿瘤异质性 

分 类 号：R686[医药卫生—骨科学]