Progression of HCV Infection to Hepatocellular Carcinoma

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June 1, 2011

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  • We examined changes in protein N-glycosylation associated with the progression of hepatitis C viral (HCV) infection to hepatocellular carcinoma (HCC). Mass spectrometric analysis of permethylated N-glycans allowed quantitative comparison of approximately hundred structures in a population of HCC cases (n=52) and cirrhotic controls (n=122) enrolled as part of an ongoing study conducted at the Institute of Transplantation, Hepatobiliary Disease and Surgery, Georgetown University Hospital. Separation of the samples into liver secreted and immunoglobulin associated fractions provided complementary information that allowed identification of N-glycans significantly elevated with liver disease and hepatocellular carcinoma. Analysis of the isolated immunoglobulins and other proteins provides specificity needed to define the association with clinical parameters. The results show that N-glycan changes differ by structural class and protein fraction. While some glycans change with age, gender or other demographic variable, major changes accompany the progression of chronic liver disease to HCC. Targeted validation of the candidate markers is under way.

    Mass Spectrometry

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