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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44CA165312-03
Application #
8712416
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lou, Xing-Jian
Project Start
2012-07-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Jbs Science, Inc.
Department
Type
DUNS #
City
Doylestown
State
PA
Country
United States
Zip Code
18902
Hann, Hie-Won; Jain, Surbhi; Park, Grace et al. (2017) Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma. Hepatoma Res 3:105-111
Chen, Dion; Jain, Surbhi; Su, Ying-Hsu et al. (2017) Building Classification Models with Combined Biomarker Tests: Application to Early Detection of Liver Cancer. J Stat Sci Appl 5:91-103
Shieh, Fwu-Shan; Jongeneel, Patrick; Steffen, Jamin D et al. (2017) ChimericSeq: An open-source, user-friendly interface for analyzing NGS data to identify and characterize viral-host chimeric sequences. PLoS One 12:e0182843
Jain, Surbhi; Xie, Lijia; Boldbaatar, Batbold et al. (2015) Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis. Hepatol Res 45:1110-23
Jain, Surbhi; Chang, Ting-Tsung; Chen, Sitong et al. (2015) Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues. Sci Rep 5:10478
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