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 50% 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 350 million people worldwide, and it is associated with more than 600,0000 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 (~50% 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 "detection f major HBV integration sites in urine" 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 (1) to develop a target-enriched NGS assay for detecting HBV-host junction sequences (HBV-JS) in urine, and (2) 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 Statement: 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.
Project Terms: Affect; AFP gene; Appearance; Area; assay development; base; Biological Assay; Biological Markers; Biotechnology; Blinded; Blood Circulation; Blood Tests; Cells; Cessation of life; Chronic Hepatitis B; Cirrhosis; Clinical; Clonal Expansion; Detection; Development; Diagnostic tests; Disease; DNA; DNA Library; DNA Markers; DNA Sequence; DR1 gene; Early Diagnosis; effective therapy; Frequencies (time pattern); Genetic; global health; Goals; GSTP1 gene; Hepatitis; Hepatitis B; Hepatitis B Virus; Hepatocyte; high risk; improved; Individual; Infection; Liver diseases; Malignant neoplasm of liver; Malignant Neoplasms; Methods; Mutation; novel; outcome forecast; Patients; Performance; Phase; phase 2 study; Population; Preventive; Primary carcinoma of the liver cells; prototype; public health relevance; Reading; reconstitution; Recurrence; research study; Risk; ROC Curve; Running; Sampling; screening; Screening for Hepatocellular Cancer; Seeds; Serum; Site; Specificity; Staging; success; Sum; Survival Rate; Testing; Tissues; TP53 gene; Translating; Ultrasonography; Urine; Vaccines; Viral; viral DNA; Virus Integration
