In this exploratory program we propose to test the hypothesis that oligosaccharides associated with serum proteins can accurately serve as biomarkers. Oligosaccharide profiles of hepatitis B surface antigens (HBsAg), purified from patient sera of different clinical populations, will be generated using novel HPLC sequencing technology that can reproducibly quantitate greater than 0.1 percent of an individual oligosaccharide in a glycan pool. Our sample population will consist of patients at risk for, or diagnosed with, hepatocellular carcinoma (HCC). The data generated will allow HBsAg oligosaccharides to be compared between different patient populations and the potential diagnostic value to be assessed. Alteration in the oligosaccharides associated with glycoproteins is one of the many molecular changes that accompany malignant transformations. In the case of HCC, an increase in fucosylation of secreted liver proteins is a common alteration. This increase in fucosylation has been postulated as a marker for HCC, however, the proteins of interest that show this alteration are typically found in low abundance (e.g. alpha fetoprotein). Our hypothesis is that, in cases where infection with hepatitis B virus (HBV) leads to the development of HCC, the viral glycoproteins (present up to mg/ml concentration) themselves may display aberrant oligosaccharides that could serve as early detection markers for HCC. Infection with HBV is the major etiology of HCC and, although HCC is a less common cancer in the USA, recent studies have shown that the incidence of HCC is rising both in the USA and worldwide. In addition, HCC is one of the most aggressive malignancies with prognosis being poor due to the late diagnosis. With the paucity of organ donors for liver transplantation and the small number of treatable patients (due to, in part, late diagnosis), early diagnosis will allow intervention at an earlier stage. We expect that this pilot study will firstly generate preliminary data to support the stated hypothesis; secondly, the study will allow the feasibility of a larger study to be determined, and thirdly, the parameters required to design a larger study to determine the value of oligosaccharide structures as potential markers of disease status will be obtained.
