N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus

Abstract

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 ␣-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.

Diagnostic Value of the Hemopexin N-Glycan Profile in Hepatocellular Carcinoma Patients

“…5). In this same narrowed patient setting, the diagnostic accuracy for the GlycoHCCtest was 62% (9%), with a sensitivity and specificity of 50% and 70%, respectively, at the published cutoff of Ϫ0.34 (12 ).…”

“…The GlycoHCCTest enables the differentiation of HBVinfected patients with HCC from cirrhosis patients, with an overall sensitivity (57%) and specificity (88%) similar to that of serum AFP (12 ). However, serum glycoproteins represent a large group of glycoproteins synthesized by both the liver and plasma cells.…”

Function characterization of a glyco-engineered anti-EGFR monoclonal antibody cetuximab in vitro

“…Whole cell ELISA showed that the recombinant wild-type EGFR mAb exhibited dose-dependent binding to A431 cells, comparable to Erbitux (Figure 1). N-glycan analysis revealed 7 dominant N-glycan structures (peaks) in the N-glycan profile, with only peak 2 and peak 7 containing bisecting GlcNAc residues [10,11] . Thus, the glycanmodified EGFR mAb with elevated abundances of peak 2 and peak 7 (bisec-EGFR mAb) was selected for further study.…”

“…Following coexpression of GnTIII and wild type EGFR mAb in this cell line, we characterized the N-glycan profile of the GnTIII-modified EGFR mAb (bisec-EGFR mAb) using DNA sequencerassisted-fluorophore-assisted capillary electrophoresis (DSA-FACE) [10,11] and quantified the α-Gal content. The effects of the EGFR mAb on cell growth, ADCC and FcγR binding capacity were investigated in vitro to assess the functions of the bisec-EGFR mAb.…”

Serum N-glycan profile shift during human ageing

“…Vanhooren et al Serum N-glycan biomarker 13 using different N-glycans from GlycoAgeTest (Callewaert et al, 2004;Liu et al, 2007). As the changes in N-glycans are a consequence of genetic and environmental influences and physiologic responses, the GlycoAgeTest marker has a significant diagnostic potential.…”