Development of a Urine Test for the Early Detection of Liver Cancer

开发用于早期检测肝癌的尿液检测

• 批准号: 8251282
• 负责人: Wei Song
• 金额: $ 24.72万
• 依托单位: JBS SCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251282
• 关键词: Alcoholism; Archives; Area; Biological Assay; Biological Markers; Biotechnology; Blinded; Blood Circulation; Blood Tests; CTNNB1 gene; Cancer Etiology; Cell Cycle; Cessation of life; Chronic Hepatitis B; Cirrhosis; Clinical; Codon Nucleotides; Commit; Cyclin D1; DNA; DNA Markers; Detection; Development; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Drops; Early Diagnosis; Epigenetic Process; Fatty Liver; Funding; Genes; Genetic; Goals; Hepatitis; Hepatitis C; Human; Hypermethylation; Image; Infection; Legal patent; Life; Liver; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Measures; Methods; Methylation; Modification; Molecular Weight; Mutation; Organ; Pathway interactions; Patients; Performance; Phase; Population; Prevalence; Primary carcinoma of the liver cells; Recurrence; Risk; Sampling; Science; Screening for Hepatocellular Cancer; Screening for cancer; Screening procedure; Seeds; Sensitivity and Specificity; Serum; Serum Markers; Site; Specificity; Staging; Surveys; Survival Rate; Testing; Tissues; Tumor Tissue; Ultrasonography; Universities; Urine; Vimentin; alpha-Fetoproteins; assay development; base; cancer type; effective therapy; high risk; improved; novel diagnostics; phase 1 study; phase 2 study; programs; prototype; research study; success; tool; tumor; Alcoholism; Archives; Area; Biological Assay; Biological Markers; Biotechnology; Blinded; Blood Circulation; Blood Tests; CTNNB1 gene; Cancer Etiology; Cell Cycle; Cessation of life; Chronic Hepatitis B; Cirrhosis; Clinical; Codon Nucleotides; Commit; Cyclin D1; DNA; DNA Markers; Detection; Development; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Drops; Early Diagnosis; Epigenetic Process; Fatty Liver; Funding; Genes; Genetic; Goals; Hepatitis; Hepatitis C; Human; Hypermethylation; Image; Infection; Legal patent; Life; Liver; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Measures; Methods; Methylation; Modification; Molecular Weight; Mutation; Organ; Pathway interactions; Patients; Performance; Phase; Population; Prevalence; Primary carcinoma of the liver cells; Recurrence; Risk; Sampling; Science; Screening for Hepatocellular Cancer; Screening for cancer; Screening procedure; Seeds; Sensitivity and Specificity; Serum; Serum Markers; Site; Specificity; Staging; Surveys; Survival Rate; Testing; Tissues; Tumor Tissue; Ultrasonography; Universities; Urine; Vimentin; alpha-Fetoproteins; assay development; base; cancer type; effective therapy; high risk; improved; novel diagnostics; phase 1 study; phase 2 study; programs; prototype; research study; success; tool; tumor

DESCRIPTION (provided by applicant): The need to develop an effective method of detecting primary and recurrent hepatocellular carcinoma (HCC) is urgent. HCC is the third leading cause of cancer deaths and has a 5-year survival rate of less than 10%. If HCC is identified early, the survival rate can be as high as 40%. The survival rate drops significantly, however, to as low as 2% if the cancer has spread to other organs. HCC is also characterized by a high recurrence rate (60%-70%). Consequently, patients with HCC must undergo imaging studies and a blood test to determine alpha- fetoprotein (AFP) levels every 6 months. The goal of this project is to explore the feasibility of a noninvasive, urine-based diagnostic test that would allow early detection of new onset and recurrent liver cancer and that would provide an effective tool for cancer management. Such a test, if applied to high-risk populations or surveyed patients, could significantly increase survival rates and could contribute to improved quality and duration of life Conventional diagnostic methods, such as ultrasound imaging and the AFP blood test, are either expensive (ultrasound) or relatively insensitive (AFP blood test). We propose a new diagnostic method, based on our progress in detecting the HCC-specific p53 mutation in the urine of patients with HCC that will enable detection of small fractions of HCC-derived genetic and epigenetically modified DNA present in the urine of patients with liver cancer. JBS Science Inc. has performed preliminary experiments that demonstrate feasibility in several key areas of this proposal. The aim will be to detect mutations in the p53 codon 249 (which is specific for HCC), and aberrant hypermethylation of the APC and GSTP-1 genes in at least 90% of the urine samples from patients whose HCC tissues are marker-positive. In phase II, we will further develop and evaluate the urine DNA test using clinical samples for the early detection of liver cancer based on the results from phase I. PUBLIC HEALTH RELEVANCE: There is a need to develop an effective method for noninvasive detection of early-stage liver cancer, which is the third leading cause of cancer deaths worldwide and has one of the highest recurrence rates. The current standard methods for screening rely on the serum level of alpha-fetoprotein, which has only 60% sensitivity. The goal of this phase I project is to explore the ability of a urine DNA test to detect early stages o liver cancer by analyzing liver cancer-associated genetic and epigenetic modifications.

描述（由申请人提供）：需要开发一种有效的方法来检测原发性和经常性肝细胞癌（HCC）的有效方法。 HCC是癌症死亡的第三大原因，其5年生存率低于10％。如果早期发现HCC，则存活率可以高达40％。但是，如果癌症扩散到其他器官，生存率显着下降至2％。 HCC还以高复发率（60％-70％）的特征。因此，HCC患者必须进行成像研究和血液检查，以确定每6个月的α-胎儿蛋白（AFP）水平。该项目的目的是探索非侵入性，基于尿液的诊断测试的可行性，该测试将允许尽早发现新发作和复发性肝癌，并为癌症管理提供有效的工具。如果应用于高风险人群或接受调查的患者，这种测试可能会显着提高存活率，并可能有助于改善寿命的质量和持续时间常规诊断方法，例如超声成像和AFP血液测试，是昂贵的（超声）或相对不敏感的（AFP血液测试）。我们提出了一种新的诊断方法，基于我们在HCC患者尿液中检测HCC特异性p53突变方面的进展，该方法将能够检测出肝癌患者尿液中hCC衍生的遗传和表观遗传修饰的DNA的小部分。 JBS Science Inc.进行了初步实验，这些实验证明了该提案的几个关键领域的可行性。目的是检测p53密码子249（特定于HCC）中的突变，以及在HCC组织中至少90％的尿液样本中，APC和GSTP-1基因的异常高甲基化。在第二阶段，我们将根据第一阶段的结果进一步开发和评估尿液DNA检测，以早日检测肝癌。 公共卫生相关性：有必要开发一种有效的方法来无创检测早期肝癌，这是全球癌症死亡的第三大主要原因，并且是复发率最高的原因之一。当前用于筛查的标准方法取决于α-蛋白质的血清水平，该方法仅具有60％的敏感性。该阶段I项目的目的是探索通过分析肝癌相关的遗传和表观遗传学修饰来检测尿液DNA检测早期O肝癌的能力。