Early Detection of Liver Cancer

描述（由申请人提供）：这是一份继续EDRN早期检测肝癌生物标志物发现实验室的提案。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志物。我们的假设，在支持的第一个时期内进行了测试，即血清多肽数量的变化或修饰与肝细胞癌（HCC）或肝炎的发病相关，已经得到证实。我们将继续开展激动人心的蛋白质组学研究，对肝癌高危人群的细胞系和人血清进行研究，其中发现了几种有前景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是一种常存的高尔基蛋白，我们发现其在血液循环中的水平与肝癌的诊断有关。与NCI联盟合作的试点研究表明，GP73水平是有待测试的肝脏疾病的最佳生物标志物之一。此外，不同的糖型似乎与组织和分泌状态有关，并可能因临床状态而异。因此，我们开发的GP73检测方法将被改进，以利用我们的新见解来提高特异性，并使其在更大规模的验证研究中具有鲁棒性，以确定人体的真实灵敏度、特异性和选择性。此外，我们在蛋白质组学和糖生物学研究中发现的新生物标志物将贡献给该管道。有希望的生物标志物水平受到抗病毒治疗影响的可能性也将被确定。根据选择性和敏感性标准选出的最有希望的候选药物将被推进到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.