Background: Immunoglobulin G and A, transferrin, haptoglobin and alpha-1-
antitrypsin represent approximately 85% of the human serum glycoproteome and their
N-glycosylation analysis may lead to the discovery of important molecular disease
markers. However, due to the labile nature of the sialic acid residues, the desialylated
subset of the serum N-glycoproteome has been traditionally utilized for diagnostic
Objective: Creating a five-protein model to deconstruct the overall N-glycosylation
fingerprints in inflammatory and malignant lung diseases.
Methods: The N-glycan pool of human serum and the five high abundant serum
glycoproteins were analyzed. Simultaneous endoglycosidase/sialidase digestion was
followed by fluorophore labeling and separation by CE-LIF to establish the model.
Pooled serum samples from patients with COPD, lung cancer (LC) and their comorbidity
were all analyzed.
Results: Nine significant (>1%) asialo-N-glycan structures were identified both in human
serum and the standard protein mixture. The core-fucosylated-agalacto-biantennary
glycan differentiated COPD and LC and both from the control and the comorbidity
groups. Decrease in the core-fucosylated-agalacto-biantennary-bisecting, monogalacto
and bigalacto structures differentiated all disease groups from the control. The
significant increase of the fucosylated-galactosylated-triantennary structure was highly
specific for LC, to a medium extent for COPD and a lesser extent for comorbidity. Also,
some increase in the afucosylated-galactosylated-biantennary structure in all three
disease types and afucosylated-galactosylated-triantennary structures in COPD and LC
were observed in comparison to the control group.
Conclusion: Our results suggested that changes in the desialylated human serum Nglycome
hold glycoprotein specific molecular diagnostic potential for malignant and
inflammatory lung diseases, which can be modeled with the five-protein mixture.