肝癌基因谱动态表达及HSPgp96异常的临床价值  

Dynamic expression of entire hepatic genomes and heat-shock protein gp96 abnormality during development of hepatocellular carcinoma

作　　者：吴信华[1] 姚登福[1] 苏小琴[1] 黄华[1] 邱历伟[1] 吴玮[1] 

机构地区：[1]南通大学附属医院医学实验中心,江苏省南通市226001

出　　处：《世界华人消化杂志》2008年第1期76-80,共5页World Chinese Journal of Digestology

基　　金：江苏医学科学重点资助项目;No.RC2003100;南通市社会发展科技计划资助项目;No.S40034~~

摘　　要：目的:探讨肝细胞癌变过程中基因表达谱的动态变化,观察热休克蛋白(HSP)gp96表达及其在肝癌早期诊断及判断预后方面的临床价值.方法:以2-乙酰氨基芴(2-FAA,0.05%)喂饲SD大鼠诱发肝癌发生,观察肝病理组织学(HE染色)改变,用全基因组芯片分析肝基因表达谱的动态变化,以巢式逆转录酶链反应扩增gp96基因片段.结果:SD大鼠在喂饲2-FAA后,肝细胞在诱癌早期发生颗粒样变性,中期出现不典型增生,后期见大量癌巢结节.肝癌发生过程中大鼠肝基因表达谱明显改变,与对照大鼠比较,癌变大鼠gp96上调3倍;诱癌变过程中,肝组织gp96 mRNA表达明显增加,变性组,癌前组和癌变组的肝组织中gp96基因表达均明显高于正常对照组(90.9%,100%,100%vs 16.67%,P<0.05).结论:肝细胞癌变过程中基因表达谱明显改变,其中gp96 mRNA呈过度表达,其分析有利于肝癌的诊断和预后判断.AIM： To investigate the dynamic expression of the entire hepatic genome during hepatocellular carcinoma （HCC） development, and the clinical values of heat-shock protein gp96 for early diagnosis of HCC and estimating its prognosis. METHODS： A rat hepatoma model was induced with 0.05% 2-acetamidoflurene （2-FAA） in male Sprague-Dawley rats. Morphological changes were observed by pathological examination （HE staining）. Total RNA was extracted from fresh liver tissues and analyzed by oligonucleotide array during liver carcinogenesis. Total RNA was transferred into cDNA by reverse transcription, and the gene fragment of gp96 was amplified by nested RT-PCR. RESULTS： Histological examination showed that hepatocytes in rats fed with 2-FAA exhibited vacuole-like denaturation at an early stage, then dysplastic nodules appeared at the middle stage, and finally progressed to cancerous nest tubercles, all of which were highly differentiated during HCC development, gp96 increased threefold in the liver of rats with HCC, compared with that of normal rats. gp96 mRNA in the liver of rats with denatured, precancerous and cancerous tissues increased compared with that in normal tissues（90.9%, 100%, 100% vs 16.67%, P 〈 0.05）. CONCLUSION： Alterations in the entire genome pattern and gp96 overexpression are observed during HCC development, gp96 may be a useful molecular marker for early diagnosis of HCC and prognosis estimation.

关 键 词：肝细胞癌 热休克蛋白GP96 基因芯片 巢式逆转录酶链反应 

分 类 号：R735.7[医药卫生—肿瘤]