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

描述（由申请人提供）：开发用于早期检测肝癌的尿液检测。因此，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，5年生存率低于15%。如果早期发现HCC，存活率可高达40%。然而，如果癌症已经扩散到其他器官，存活率会显著下降至2%。该项目的目标是开发一种非侵入性的，基于尿液的诊断测试，可以早期发现肝癌。这种测试，如果应用于高风险人群或调查患者，可以显着提高生存率，并可能有助于提高生活质量和寿命。传统的诊断方法，如超声成像和AFP血液检测，要么昂贵（超声），要么相对不敏感（AFP血液检测，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小部分HCC衍生的遗传和表观遗传修饰的DNA。JBS Science Inc.成功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尿液检测的灵敏度约为80%，特异性为90%，并且能够在一项使用存档尿液DNA样本的良好对照的开放标记研究中检测到约90%的AFP阴性HCC，其代表约50%的HCC。这项II期研究的目标是进一步开发尿液检测，以在盲法预验证研究中检测早期（I/II期）HCC患者至少90%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.