Glycomic alterations in the highly-abundant and lesser-abundant blood serum protein fractions for patients diagnosed with hepatocellular carcinoma

Hepatocellular cancer (HCC) is a serious human disease with an unfortunately low survival rate. It further poses a significant epidemic threat to our society through its viral vectors associated with cirrhosis conditions preceding the cancer. A search for biomarkers of these diseases enlists analytical glycobiology, in general, and quantitative biomolecular mass spectrometry (MS), in particular, as valuable approaches to cancer research. The recent advances in quantitative glycan permethylation prior to MALDI-MS oligosaccharide profiling has enabled us to compare the glycan quantitative proportions in the small serum samples of cancer and cirrhotic patients against control individuals. In this investigation, reasoning that some of the observed glycomic changes could be at least partly explained by acute-phase or immune responses, we further fractionated the major serum proteins from the minor components and compared statistically their differential glycosylation, elucidating some causes of quantitatively unusual glycosylation events. Numerous glycan structures were identified and tentatively connected with their originating proteins, with a particular emphasis on sialylated and fucosylated glycans. In particular, for the highly-abundant protein fraction, several smaller, neutral glycans were observed to be different between disease-free individuals and those diagnosed with either HCC or cirrhosis. Further, these types of glycans were also different between the two diseases. In the lesser-abundant protein fraction, a number of sialylated glycans were different between each state-of-health.