Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

N-linked glycan branching and fucosylation are increased directly in hepatocellular carcinoma tissue as determined through in situ glycan imaging and are associated with poor outcome (#912)

Connor A West 1 , Mengjun Wang 1 , Richard R Drake 1 , Anand S Mehta 1
  1. Medical University of South Carolina, Charleston, SOUTH CAROLINA, United States

Hepatocellular carcinoma (HCC) remains the fifth most common cancer worldwide and accounts for approximately 700,000 deaths annually. Changes in serum glycosylation have long been associated with HCC but the source material is unknown and direct glycan analysis of HCC tissues has been limited. Our laboratory previously developed a method of in situ tissue based N-linked glycan imaging that bypasses the need for microdissection and solubilization of tissue prior to analysis. We used this methodology in the analysis of 138 HCC tissue samples and compared the N-linked glycans in cancer tissue with either adjacent untransformed or cirrhotic tissue. Post analysis, there were over 75 N-linked glycans found to be associated with HCC. Ten glycans were found significantly elevated in HCC tissues compared to cirrhotic or adjacent tissue and fell into two major classes: increased fucosylation and increased branching. In analysis of 90 tissue pairs (HCC and adjacent un-transformed tissue), these classes were associated with poor outcome with high levels of branched and singly or doubly fucosylated glycans resulted in a median survival time of 25 months, as compared to patients with low levels having a median survival time of 35 months and 32 months respectively. When patients with early HCC were examined, the five-year survival rate of those with high levels of the tetra-antennary glycan with a single fucose residue was 23% less than those with low levels, and a more striking difference of 40% less when looking at two-year survival times. These 90 tissue pairs were then evaluated for core versus outer arm fucosylation via Endoglycosidase F3 imaging to determine the relevance of fucosylation linkages on survival and outcome data while maintaining spatial localization. This work marks one of the first spatially localized glycomic evaluations of HCC tissue directly as compared to un-transformed adjacent tissue with included survival outcomes.