HCC diagnostics defined by fucosylated serum biomarkers

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop a novel early detection diagnostic for hepatocellular carcinoma based on the detection of glycoproteins that have increased levels of fucosylation in the sera of patients. With our colleagues at Drexel University, we have shown that there is an increase in the level of core fucosylation associated with the development of liver cancer. The observation that changes in glycosylation patterns occur with cancer has been reported earlier by others as well, however, currently, no novel fucosylated glycoprotein is being developed as diagnostics. In our earlier studies, we identified a number of glycoproteins with elevated levels of fucosylation and validated 3 such proteins for further diagnostics development. The objectives of this phase I is to develop a Lectin-ELISA assay and validate the assay with a small cohort of patients diagnosed with HCC. In phase II, the specificity and sensitivity of the assay will be evaluated using a large serial and cross sectional patient population and compared with the existing diagnostic assay for HCC to generate clinical data needed for an approval of a new in vitro diagnostic test for HCC. Accomplishments of these aims will permit the introduction of a highly sensitive and specific diagnostic tool for the early detection of HCC. Given the need for early diagnosis for HCC to facilitate early intervention that can lead to a cure, the introduction of a new non-invasive, high through put and highly sensitive and specific diagnostic based on hyperfucosylated serum markers as described here is extremely important. Hepatocellular carcinoma (HCC) is one of the most common solid malignancies worldwide and the incidence in the United States is increasing. Approximately two-thirds of all liver cancers are HCC, one of the most common aggressive malignancies. The number of cases of HCC will continue to increase primarily due to the hepatitis C (HCV) epidemic. Despite advances in medical technology, the 5-year survival between 1981 and 1998 improved only 3%, likely due to the fact that the majority of patients with HCC are diagnosed at advanced stages leading to an overall 1-year survival of 25% in the United States. In this setting of a significant increase in the number of patients with HCC, early detection and treatment are vital to improve outcome.