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

描述（由申请人提供）：开发一种早期检测肝癌的尿检方法。迫切需要开发一种有效的检测肝细胞癌（HCC）的方法。HCC是癌症死亡的第三大原因，其5年生存率不到15%。如果早期发现HCC，生存率可高达40%。然而，如果癌症扩散到其他器官，生存率会显著下降，低至2%。这个项目的目标是开发一种无创的、基于尿液的诊断测试，从而可以早期发现肝癌。如果将这种测试应用于高风险人群或接受调查的患者，可以显著提高生存率，并有助于改善生活质量和延长生活时间。传统的诊断方法，如超声成像和甲胎蛋白血液检查，要么价格昂贵（超声），要么相对不敏感（甲胎蛋白血液检查，对早期（I/II） HCC的敏感性为25-50%）。我们提出了一种新的诊断方法，基于我们的I期3标记尿液检测，用于检测肝癌患者尿液中存在的少量hcc衍生遗传和表观遗传修饰DNA。JBS科学公司已经成功地完成了第一阶段的研究，证明了该提案在几个关键领域的可行性。令人鼓舞的是，JBS I期HCC尿液检测的灵敏度为80%，特异性为90%，并且能够检测到约90%的afp阴性HCC，占约50%的HCC，这是一项控制良好的开放标记研究，使用存档的尿液DNA样本。这项II期研究的目标是进一步发展尿液检测，在盲法预验证研究中检测至少90%的早期（I/II期）HCC患者的尿液样本，并获得足够的信息，为大型多中心验证研究做准备。

DESCRIPTION (provided by applicant): Development of a urine test for the early detection of liver cancer. The need to develop an effective method of detecting hepatocellular carcinoma (HCC) is urgent. HCC is the third leading cause of cancer deaths and has a 5-year survival rate of less than 15%. 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. The goal of this project is to develop a noninvasive, urine-based diagnostic test that would allow for early detection of liver cancer. Such a test, if applied to high-risk populations o 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, 25-50% sensitivity to early stage (I/II) HCC). We propose a new diagnostic method, based on our phase I 3-marker urine test for detecting small fractions of HCC-derived genetically and epigenetically modified DNA present in the urine of patients with liver cancer. JBS Science Inc. has successfully accomplished the phase I study that demonstrates feasibility in several key areas of this proposal. Encouragingly, the JBS phase I HCC urine test had a sensitivity of ~80% and a specificity of 90% and was able to detect ~90% of AFP-negative HCC, which represents ~50% of HCC, in a well-controlled, open labeled study using archived urine DNA samples. The goal of this phase II study is to further develop the urine test to detect at least 90% of the urin samples from patients with early stage (stages I/II) HCC in a blinded pre-validation study and obtain sufficient information to prepare for a large multicenter validation study.