Tong Guang-Dong, Zhou Da-Qiao, He Jin-Song, Xiao Chun-Ling, Liu Xin-Liang, Zhou Xiao-Zhou, Zhang Xi, Xing Yu-Feng, Lü Ping, Feitelson Mark A
Department of Liver Diseases, Affiliated Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen 518033, China.
Zhonghua Gan Zang Bing Za Zhi. 2007 Nov;15(11):828-32.
To identify serologic markers that may indicate the early presence of hepatocellular carcinoma (HCC), and analyze their significance in the pathogenesis of chronic hepatitis B.
Hepatitis B x antigen (HBxAg) positive and negative HepG2 cells were subjected to PCR select cDNA subtraction 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, Sui1. 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 carriers 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.
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-Sui1 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.
These antibodies can be detected in serum samples several months to several years before the appearance of HCC. This suggests that they may be preneoplastic markers that may help to distinguish which HBV carriers with cirrhosis are most likely to progress and develop HCC.
鉴定可能提示肝细胞癌（HCC）早期存在的血清学标志物，并分析其在慢性乙型肝炎发病机制中的意义。
对乙型肝炎x抗原（HBxAg）阳性和阴性的HepG2细胞进行PCR选择性cDNA扣除，以鉴定可能在HCC发生之前差异表达的基因。这些基因包括上调基因URG4、URG7、URG11和VEGFR3，以及下调基因Sui1。构建特异性酶联免疫吸附测定（ELISA）来检测差异表达的抗原及其相应抗体，以确定它们是否具有预后和/或诊断价值。研究人群包括730人。其中，416人为HBsAg（-），298人为患有慢性肝病和/或HCC的HBV携带者。此外，16例患者患有非病毒性肝炎。其中，收集并研究了53例HBsAg（+）肝硬化患者的系列血清样本。
在HBV相关肝硬化和HCC患者的血清样本中可检测到针对多个差异调节基因的抗体，但在未感染个体的血清样本中未检测到（P<0.01）。在无肝病的HBV患者的血清样本、其他肿瘤类型患者的血清样本以及非病毒性肝炎患者的血清样本中均未检测到抗体。在发生HCC风险较高的患者中，发现这些抗体与国籍和种族无关。对28例HBsAg（+）HCC患者的统计分析表明，抗URG11和抗VEGFR3是最常检测到的抗体。发现这些抗体在16例患者中共存（P<0.05）。相比之下，在25例无HCC的HBsAg（+）患者中，抗Sui1和抗URG7是最普遍的抗体。这些抗体在11例患者中共存（P<0.05）。此外，在HCC出现之前检测到四种或更多抗体的HCC患者生存结局较差。
这些抗体可在HCC出现前数月至数年的血清样本中检测到。这表明它们可能是癌前标志物，有助于区分哪些肝硬化HBV携带者最有可能进展并发展为HCC。
