不同转移潜能人肝癌模型血清蛋白质组学研究  

Serum proteomic analysis of human hepatocellular carcinomas with different metastatic potentials

作　　者：伍龙[1] 侯晋轩[1] 彭春伟[1] 张燕华[1] 陈良冬[1] 李雁[1] 

机构地区：[1]武汉大学中南医院肿瘤科肿瘤生物学行为湖北省重点实验室,430071

出　　处：《中华实验外科杂志》2010年第10期1448-1450,1564,共4页Chinese Journal of Experimental Surgery

基　　金：基金项目：教育部新世纪优秀人才支持计划资助项目（NCET-04-0669）;全国优秀博士学位论文作者专项资金资助项目（200464）;国家自然科学基金资助项目（20675058）;国家自然科学基金委创新研究群体科学基金资助项目（20621502）;国家科技重大专项资助项目（2008ZXl0002-021）

摘　　要：目的 采用血清蛋白质组学技术筛选并鉴定肝癌转移相关的蛋白分子.方法 建立不同转移潜能人肝癌HCCLM9和MHCC97L动物模型各8只,采用双向凝胶电泳和MALDI串联飞行时间质谱仪（MALDI-TOF/TOF）技术比较和鉴定差异表达的血清蛋白分子,Western blot和动物模型标本验证后,进一步对208例临床标本（男性170例,女性38例）验证.结果 HCCLM9和MHCC97L组比较,血清蛋白表达显著差异达11个,其中补体因子H（CFH）在HCCLM9模型血清中水平（213.83±55.17）是MHCC97L组（122.48±48.91）的1.75倍.裸鼠肝癌组织中免疫组织化学提示CFH表达明显升高.208例临床病理组织显示,CFH表达越强,临床病期越晚.结论 CFH与肝癌侵袭转移相关.Objective Serum proteomics approaches were applied to search for and validate hepatocellular carcinoma （HCC） invasion- and metastasis-related biomarkers. Methods Sixteen male athymic BALB/C nu/nu mice were randomly divided into two groups. HCCLM9-and MHCC97L-nude mice models of human HCC, with a similar genetic background and remarkably different pulmonary metastasis potential,were established. 2D gel electrophoresis （2-DE） and MALDI-TOF/TOF technologies were used to construct a comparative proteome profile of nude mice sera from HCCLM9- and MHCC97L-nude mice. Candidate protein was confirmed by Western blotting on serum, immunohistochemistry （IHC） on animal tumor tissues, and tissue micro-array on clinical specimens including 170 male cases and 38 female cases. Results Serum proteins from HCCLM9- and MHCC97L-nude mice were compared by 2-DE. A total of 11 proteins were identified by MALDI-TOF/TOF. Complement factor H （CFH） was overexpressed in HCCLM9- （213.83 ± 55.17） versus MHCC97L-nude mice serum （122.48 ±48.91 ） by Western blotting,and validated by IHC from both nude mice tumor tissues and clinical specimens. Elevated CFH expression was observed in liver cancer tissues of HCCLM9 nude mice. IHC study in 208 human HCC specimens demonstrated that patients with higher CFH expession showed greater invasiveness and more advanced stage.Conclusion CFH may be a candidate biomarker to predict HCC invasive behavior.

关 键 词：补体因子H 血清 蛋白质组学 癌 肝细胞 

分 类 号：R735.7[医药卫生—肿瘤]