Detection of major HBV integration sites in urine as a biomarker for HBV-associated liver cancer

DESCRIPTION provided by applicant Detection of major HBV integration sites in urine as a biomarker for HBV associated liver cancer This Phase I application is to test the feasibility of using the appearance of major HBV integration sites the viral host junction DNA sequences in the urine of patients infected with the hepatitis B virus HBV as a DNA biomarker for the early detection of HBV associated hepatocellular carcinoma HBV HCC HBV is a major etiological agent that causes more than of hepatocellular carcinoma HCC cases worldwide Despite the availability of a preventive vaccine chronic hepatitis B infection remains a global health issue affecting more than million people worldwide and it is associated with more than deaths annually most of which are due to the development of HBV HCC Although HCC surveillance is implemented for this well defined high risk HBV infected population most HBV HCC remains undetected until late stages by current screening methods such as expensive ultrasound imaging and the insensitive sensitivity AFP blood test Therefore there is an urgent need for a more sensitive biomarker for detecting primary and recurrent HCC The goal of this project is to explore the viability of translating our novel biomarker andquot detection f major HBV integration sites in urineandquot to a noninvasive urine based diagnostic test a UsDx HBV HCC urine DNA test that would allow early detection of new and recurrent HBV HCCs We have detected HCC derived genetic and epigenetically modified DNA in the urine of patients with liver cancer U Screen Dx Inc has performed preliminary experiments that demonstrate the feasibility of this proposal in several key areas The aims are to develop a target enriched NGS assay for detecting HBV host junction sequences HBV JS in urine and to evaluate the appearance of major HBV JS in urine as a biomarker for distinguishing HBV HCC from other liver diseases in HBV infected subjects If successful we will further develop and evaluate the HBV HCC urine DNA test using clinical samples for the early detection of liver cancer in the high risk HBV infected population in Phase II PUBLIC HEALTH RELEVANCE The goal of this study is to explore the feasibility that detection of the major HBV host junction sequences in the circulation can be a biomarker for the early detection of HBV associated HCC Such marker will enable high risk groups such as those chronically infected with HBV to be screened for liver cancer with higher sensitivity thus permitting for early detection of the liver cancer so the prognosis of the disease can be improved