Early antibody markers of HCC

HCC 早期抗体标志物

• 批准号: 7102620
• 负责人: MARK A FEITELSON
• 金额: $ 27.71万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102620
• 关键词: African; Chinese; biomarker; cancer risk; clinical research; diagnosis design /evaluation; disease carrier state; early diagnosis; enzyme linked immunosorbent assay; hepatitis B; hepatitis B antigens; hepatitis B virus group; hepatocellular carcinoma; human population genetics; human tissue; laboratory rabbit; neoplasm /cancer diagnosis; neoplasm /cancer epidemiology; prognosis; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): Hepatitis B virus (HBV) encoded x antigen (HBxAg) is a trans-activating protein that contributes to the development of hepatocellular carcinoma (HCC) by altering expression of selected hepatocellular genes. To identify some of these genes, HBxAg or vector were introduced into the human hepatoblastoma cell line, HepG2, and differentially expressed genes were identified by PCR select cDNA subtraction. Differential expression of these genes was verified by in situ hybridization (ISH) and immunohistochemistry (IHC) of HBV infected compared to uninfected liver samples. Costaining of HBxAg with several up-regulated proteins implies that each may be up-regulated by HBxAg or be a cellular response to HBxAg in vivo. To determine whether these up-regulated gene (URG) products or corresponding antibodies to them exist in serum, appropriate ELISAs were designed. In retrospective longitudinal studies, antibodies to multiple URGs were detected in the sera from 23 of 25 (>90%) of Korean carriers with HCC an average of 3 years prior to tumor diagnosis, in 18 of 24 (75%) of Korean carriers with dysplastic and/or regenerative nodules but no HCC, and in < 15% of asymptomatic carriers. Additional cross-sectional and longitudinal prospective studies in other carrier populations are required to validate these markers. Hence, the objective of this proposal will be to establish the clinical utility of these antibodies in various HBV carrier populations at risk for the development of HCC. Given that Chinese and African patients come from regions of the world with the highest incidence of HBV infection and HCC, cross-sectional (aim 1) and longitudinal (aim 2) studies will be conducted to determine whether these markers are prevalent in tumor bearing patients and/or in those at high risk for tumor development, respectively. Additional work will determine the specificity of these markers using serum samples from patients who are not HBV infected (aim 3). Antibodies to other HBxAg URGs will also be tested to optimize the sensitivity, specificity and predictive value; of the antibody panel (aim 4). This work will establish a rapid, simple, inexpensive and noninvasive blood test for early HCC that will save many lives by permiting early detection and curative intervention.

描述（由申请人提供）： B型肝炎病毒（HBV）编码的X抗原（HBxAg）是一种反式激活蛋白，其通过改变选定的肝细胞基因的表达而促成肝细胞癌（HCC）的发展。为了鉴定其中的一些基因，将HBxAg或载体导入人肝母细胞瘤细胞系HepG 2，并通过PCR选择cDNA消减法鉴定差异表达的基因。通过原位杂交（ISH）和免疫组化（IHC）的HBV感染的肝样品相比，未感染的肝样品，这些基因的差异表达进行了验证。HBxAg与几种上调蛋白的共染色表明，每种蛋白都可能被HBxAg上调，或者是体内对HBxAg的细胞反应。为了确定这些上调的基因（URG）产物或其相应的抗体是否存在于血清中，设计了适当的ELISA。在回顾性纵向研究中，在肿瘤诊断前平均3年的25名韩国HCC携带者中的23名（>90%）、24名具有异型增生和/或再生结节但无HCC的韩国携带者中的18名（75%）和< 15%的无症状携带者的血清中检测到多种URG抗体。需要在其他携带者人群中进行额外的横断面和纵向前瞻性研究来验证这些标志物。因此，本提案的目的是确定这些抗体在各种HBV携带者人群中的临床效用，这些人群有发生HCC的风险。鉴于中国和非洲患者来自世界上HBV感染和HCC发病率最高的地区，将进行横断面（目标1）和纵向（目标2）研究，以确定这些标志物是否分别在肿瘤患者和/或肿瘤发生高风险患者中普遍存在。进一步的工作将使用未感染HBV的患者的血清样本确定这些标志物的特异性（目的3）。还将检测其他HBxAg URG的抗体，以优化抗体组的灵敏度、特异性和预测值（目的4）。这项工作将建立一个快速，简单，廉价和非侵入性的血液检测早期肝癌，将挽救许多生命的早期发现和治疗干预。