We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by alpha-fetoprotein (AFP) analysis, ultrasonography, and/or computed tomography and was studied histologically. N-glycan profiles of serum proteins were determined with DNA sequencer-based carbohydrate analytical profiling technology. In this study, we found that a branch alpha(1,3)-fucosylated triantennary glycan was more abundant in patients with HCC than in patients with cirrhosis, patients with fibrosis, and healthy blood donors, whereas a bisecting core alpha(1,6)-fucosylated biantennary glycan was elevated in patients with cirrhosis. The concentration of these 2 glycans and the log ratio of peak 9 to peak 7 (renamed the GlycoHCCTest) were associated with the tumor stage. Moreover, for screening patients with HCC from patients with cirrhosis, the overall sensitivity and specificity of the GlycoHCCTest were very similar to those of AFP.
Conclusion: This study indicates that a branch alpha(1,3)-fucosylated glycan is associated with the development of HCC. The serum N-glycan profile is a promising noninvasive method for detecting HCC in patients with cirrhosis and could be a valuable supplement to AFP in the diagnosis of HCC in HBV-infected patients with liver cirrhosis. Its use for the screening, follow-up, and management of patients with cirrhosis and HCC should be evaluated further.