乙型肝炎相关肝癌的癌前病变标志物检测及其意义  

Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma and their significance inclinical settings

作　　者：童光东[1] 周大桥[1] 贺劲松[1] 肖春玲[1] 刘心亮[1] 周小舟[1] 张希[1] 邢宇锋[1] 吕屏 Mark A．Feitelson 

机构地区：[1]广州中医药大学附属深圳医院肝病科,518033 [2]Department of Biology,College of Science and Technology,Temple University,Philadelphia,PA 19122 USA

出　　处：《中华肝脏病杂志》2007年第11期828-832,共5页Chinese Journal of Hepatology

基　　金：国家自然科学基金（30371790）;广东省自然科学基金（C03050301）;深圳市科技局项目（200304145）

摘　　要：目的探讨乙型肝炎相关的肝癌前病变标志物及其临床意义。方法在X基因阳性与阴性的HepG2细胞系中，通过抑制性cDNA差减杂交，建立特异性ELISA方法，对深圳及美国的韩国裔移民730人血清检测肝癌变前标志物抗体（抗-URG4、抗-URG7、抗-URG11、抗-URG12、抗-VEGFR3和抗-Suil）。730人中HBsAg阴性者416名、慢性HBV感染者298例、其他肝炎患者16例。另外对其中53例乙型肝炎肝硬化患者进行3～5年的临床观察。结果HBsAg阴性者6个抗体阳性率与乙型肝炎肝硬化、肝癌患者比较，差异有统计学意义（P值均〈0．01），而与HBV携带者、非肝癌和非病毒性肝炎患者相比，差异均无统计学意义（P值均〉0．05）。而且，这些抗体发生率在高危人群中，与种族、国家、地区无相关性。临床观察显示：53例乙型肝炎肝硬化患者中28例发展成肝癌，其肝癌发生前抗-URG11和抗-VEGFR3同时阳性者16例（P〈0．05）；未发生癌变的25例肝硬化患者中，11例抗-URG7、抗-Suil同时阳性（P〈0．05）。此外，在发生肝癌之前检测到4个或更多抗体的患者，其生存期较短。结论6个抗体可在肝癌发生数月或数年前就能被检测到，提示它们可能是肝癌癌前病变重要的标志物，用它们预测肝癌的发生与预后，可能会使通过血清AFP检测诊断小肝癌提前到诊断癌前病变。Objective To identify serologic markers that may indicate the early presence of hepato-cellular carcinoma （HCC）, and analyze their significance in the pathogenesis of chronic hepatitis B. Methods Hepatitis B x antigen （HBxAg） positive and negative HepG2 cells were subjected to PCR select cDNA sub-traction to identify differentially expressed genes that may precede the development of HCC. These included the up-regulated genes URG4, URG7, URG11, and VEGFR3, and the down-regulated gene, Suil. Specific ELISAs were constructed to measure differentially expressed antigens and their corresponding antibodies to determine whether they had prognostic and/or diagnostic value. The study population consisted of 730 people. Among them, 416 were HBsAg（-） and 298 were HBV carders with chronic liver disease and/or HCC. In addition, 16 patients had non-viral hepatitis. Among these, serial serum samples from 53 HBsAg（＋） patients with cirrhosis were collected and studied. Results Antibodies to multiple differentially regulated genes were detectable in serum samples from patients with HBV associated cirrhosis and HCC, but not in serum samples from uninfected individuals （P〈0.01）. Antibodies were undetectable in serum samples from HBV patients without liver disease and in serum samples from patients with other tumor types, and among those with non viral hepatitis. Among patients at high risk of developing HCC, these antibodies were found to be independent of nationality and ethnicity. Statistical analysis of the 28 HBsAg（＋） patients with HCC showed that anti-URG11 and anti-VEGFR3 were the most frequently detected antibodies. These antibodies were found to coexist in 16 （P〈0.05）. In contrast, among the 25 HBsAg（＋） patients without HCC, anti-Suil and anti-URG7 were the most prevalent antibodies. These antibodies coexisted in 11 （P〈0.05）. In addition, HCC patients with four or more antibodies detected before the appearance of HCC had a poorer survival outcome. Conclusion These antibodies ca

关 键 词：癌 肝细胞 抗体 肝炎 乙型 慢性 标志物 癌前病变 

分 类 号：R686[医药卫生—骨科学]