Glycosylation and Liver Cancer

Abstract

Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development.

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

“…Alterations of serum core fucosylation, outer-arm fucosylation, increased sialylation, and glycan branching were described in patients with HCC. Similar findings have been found directly in HCC tissue, suggesting that these glycan changes may play a role in tumor formation and development (115).…”

Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC

“…Indeed, in the most recent Annual Report to the Nation on the Status of Cancer, HCC had the second fastest rise in incidence and the greatest increase in mortality among both men and women(1). HCC incidence is predicted to continue rising in the United States and exceed 50,000 cases per year by 2025(2). …”

Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation

“…HCC is one of the most common solid malignancies worldwide, and the incidence in the United States is increasing2. In this setting of a significant increase in the number of patients with HCC, early detection and treatment are vital to improve the otherwise dismal outcome of this disease34.…”