Early Detection of Liver Cancer

肝癌的早期发现

• 批准号: 7913929
• 负责人: Timothy M Block
• 金额: $ 16.79万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7913929
• 关键词: Alcoholic Liver Diseases; Antiviral Agents; Antiviral Therapy; Biological Assay; Biological Markers; Blood Circulation; Clinical; Detection; Development; Diagnosis; Disease; Early Detection Research Network; Early Diagnosis; Glycobiology; Glycoproteins; Goals; Golgi Apparatus; Hepatitis; Hepatitis B Virus; Hepatitis C virus; Human Cell Line; Individual; Laboratories; Liver; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Methods; Modeling; Modification; Nature; Pathway interactions; Pilot Projects; Population; Population Heterogeneity; Population Study; Predictive Value; Primary carcinoma of the liver cells; Protein Isoforms; Proteins; Proteomics; Research; Risk; Sampling; Schedule; Screening for Hepatocellular Cancer; Screening procedure; Sensitivity and Specificity; Serum; Source; Specificity; Staging; Technology; Testing; Time; TimeLine; Tissues; Validation; Work; base; cancer diagnosis; cancer risk; drug development; feeding; improved; insight; non-alcoholic; polypeptide; validation studies

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.

描述（由申请人提供）：这是一项继续EDRN肝癌生物标志物发现实验室早期检测的提案。我们的总体目标是识别和开发用于早期检测肝癌的生物标志物。我们的假设，在第一个支持期内进行了测试，即血清多肽的量或修饰的变化与肝细胞癌（HCC）或肝炎的发生相关，已得到证实。我们将建立在我们令人兴奋的细胞系和人类血清的蛋白质组学研究的基础上，这些研究来自肝癌风险人群，其中发现了几种有前途的方法和生物标志物线索。例如，我们将确定GP73（一种常驻高尔基体蛋白，我们发现其在循环中的水平与肝癌诊断相关）可用作疾病生物标志物的可能性。与NCI财团合作的试点研究表明，GP73水平是待检测的肝病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相关，并且其本身可能随临床状态而变化。因此，我们开发的GP73检测方法将得到改进，以利用我们的新见解来提高特异性，并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，我们的蛋白质组学和糖生物学研究发现的新生物标志物将有助于管道。也将确定有希望的生物标志物水平受抗病毒治疗影响的可能性。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验证阶段，以确定最终的效用。