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.

Public Health Relevance

The need is urgent to have an effective method for noninvasive detection of early-stage liver cancer, which is the third leading cause of cancer death 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 ~50% sensitivity. The goal of this project is to develop a urine DNA test to detect early stages of liver cancer by analyzing liver cancer-associated genetic and epigenetic modifications.

National Institute of Health (NIH)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1)
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Lou, Xing-Jian
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Jbs Science, Inc.
United States
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Su, Ying-Hsiu; Lin, Selena Y; Song, Wei et al. (2014) DNA markers in molecular diagnostics for hepatocellular carcinoma. Expert Rev Mol Diagn 14:803-17