The need to develop an effective method of detecting primary and recurrent hepatocellular carcinoma (HCC) is urgent. HCC is the third leading cause of cancer deaths and has a 5-year survival rate of less than 10%. 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. HCC is also characterized by a high recurrence rate (60%-70%). Consequently, patients with HCC must undergo imaging studies and a blood test to determine alpha- fetoprotein (AFP) levels every 6 months. The goal of this project is to explore the feasibility of a noninvasive, urine-based diagnostic test that would allow early detection of new onset and recurrent liver cancer and that would provide an effective tool for cancer management. Such a test, if applied to high-risk populations or 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). We propose a new diagnostic method, based on our progress in detecting the HCC-specific p53 mutation in the urine of patients with HCC that will enable detection of small fractions of HCC-derived genetic and epigenetically modified DNA present in the urine of patients with liver cancer. JBS Science Inc. has performed preliminary experiments that demonstrate feasibility in several key areas of this proposal.
The aim will be to detect mutations in the p53 codon 249 (which is specific for HCC), and aberrant hypermethylation of the APC and GSTP-1 genes in at least 90% of the urine samples from patients whose HCC tissues are marker-positive. In phase II, we will further develop and evaluate the urine DNA test using clinical samples for the early detection of liver cancer based on the results from phase I.
There is a need to develop an effective method for noninvasive detection of early-stage liver cancer, which is the third leading cause of cancer deaths 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 60% sensitivity. The goal of this phase I project is to explore the ability of a urine DNA test to detect early stages o liver cancer by analyzing liver cancer-associated genetic and epigenetic modifications.
|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|
|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|