Early Detection of Liver Cancer

描述(申请人提供)：这是一项继续EDRN的肝癌生物标志物发现实验室的早期检测的建议。我们的总体目标是识别和开发用于肝癌早期检测的生物标记物。我们的假设，在支持的第一阶段进行了测试，即血清多肽的数量或修饰的变化与肝细胞癌(HCC)或肝炎的发病相关，这一假设已得到证实。我们将对肝癌高危人群的细胞系和人血清进行令人兴奋的初步蛋白质组学研究，在这些研究中发现了几种有希望的方法和生物标志物线索。例如，我们将确定GP73作为疾病的生物标志物的可能性。GP73是一种常驻高尔基蛋白，我们发现其循环中的水平与肝癌的诊断有关。与NCI联盟合作的初步研究表明，GP73水平是有待测试的最佳肝病生物标志物之一。此外，不同的糖形式似乎与组织和分泌状态有关，并且本身可能随着临床状态的不同而不同。因此，我们开发的GP73检测分析将进行改进，以利用我们的新见解来提高特异性，并使其适用于更大规模的验证研究，以确定人的真实敏感度、特异度和选择性。此外，我们的蛋白质组和糖生物学研究发现的新生物标记物将有助于管道的建设。有希望的生物标记物水平受到抗病毒治疗影响的可能性也将得到确定。根据选择性和敏感性标准选出的最有希望的候选者将进入最终效用确定的验证阶段。

DESCRIPTION (provided by applicant): This is a proposal to continue the Early Detection of Liver Cancer Biomarker Discovery Laboratory of the EDRN. Our over-all goal has been to identify and develop biomarkers for the early detection of liver cancer. Our hypothesis, tested within the first period of support, that changes in the amount or modification of serum polypeptides correlate with the onset of hepatocellular carcinoma (HCC) or hepatitis, has been confirmed. We will build upon our exciting initial proteomic studies of cell lines and human serum derived from those at risk for liver cancer in which several promising approaches and biomarker leads were found. For example, we will determine the possibility that GP73, a resident Golgi protein whose level in the circulation was found by us to correlate with a diagnosis of liver cancer, can be used as a biomarker of disease. Pilot studies, in cooperation with NCI consortia, showed that GP73 levels were among the best biomarkers of liver disease to be tested. Moreover, different glycoforms appeared to be associated with tissue and secreted states and may in themselves vary with clinical status. Therefore, the GP73 detection assay, developed by us, will be refined to exploit our new insights to improve specificity, and made robust for larger validation studies to determine true sensitivity, specificity and selectivity, in people. In addition, new biomarkers discovered by our proteomic and glycobiology research will be contributed to the pipeline. The possibility that promising biomarker levels are influenced by antiviral therapy will also be determined. The most promising candidates, chosen on the basis of selectivity and sensitivity criteria, will be advanced to the validation stage for ultimate utility determination.