Glycosylation changes in hepatocellular carcinoma

A68

Increasing incidence of hepatocellular carcinoma (HCC) was associated with hepatitis C (HCV) viral infection. Our study of HCC in Egypt, a country with an epidemic of HCV, identified a set of glycans as candidate markers for early detection of HCC. Glycans enzymatically released from serum proteins were analyzed by MALDI-TOF/TOF following solid phase permethylation. Analysis of less than 0.05 ml of serum allowed relative quantification of 80 glycans. Approximately half of the glycans changed significantly at p<0.01 in HCC patients (n=73) compared to matched control with liver cirrhosis (n=52). A set of only 3 glycans was sufficient to classify HCC with 93 % prediction accuracy in a blinded validation set of samples (n=75). The differences were confirmed by a multivariate regression analysis adjusting for age, gender, and other important covariates. Other glycans change abundance already at earlier stage of progression of HCV infection to HCC and could be used to track the natural progression of the disease. The structure of the glycans suggests which glycosylation processes are affected in the pathophysiology of liver disease. In conclusion, aberrant glycosylation of serum proteins in liver disease can be quantified by mass spectrometric analysis of permethylated glycans. The glycans represent a very promising candidate marker for early detection of HCC.