Glycosylation and liver cancer

Abstract

Liver cancer is the fifth most common cancer, but the second 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 or hepatitis C virus infection. While chronic viral infection remains the main cause of liver disease and risk of hepatocellular carcinoma (HCC), rates of nonviral-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.

Keywords: Fucosylation; Glycomics; Glycoproteomics; Glycosylation; Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Liver cancer; Nash.

Figure 1

Rates of liver and intrahepatic bile duct cancer in the United States in from 1990 to 2014. Data is based upon the SEER Cancer Statistics Review (CSR) 1975–2011 and the NCI web-site on liver cancer (http://www.cancer.gov/cancertopics/types/liver).

Figure 2

Lectin staining of HCC or adjacent normal tissue with a recombinant Aleuria aurantia lectin (AAL) that has greater affinity for core fucosylated glycan. Panels A (4X) and B (20x) are from tissue adjacent to the HCC. Areas of staining indicated with the asterisks are the liver sinusoids, which stain with the core fucose binding lectin. Panels C (4X) and D (20x) are from the HCC tissue. In addition to the liver sinusoids, which stain with the core fucose binding lectin as in panels A and B, defined staining of hepatocytes, as indicted by the arrows, can also be seen.