Title:Modeling of the Desialylated Human Serum N-glycome for Molecular Diagnostic Applications in Inflammatory and Malignant Lung Diseases
VOLUME: 20 ISSUE: 10
Author(s):Anna Farkas, Brigitta Mészáros, Máté Szarka, Márton Szigeti, János Kappelmayer, Miklós Szabó, Eszter Csánky and András Guttman*
Affiliation:Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Doctoral School of Molecular Medicine, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Egyetem ter 1, Debrecen, Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Doctoral School of Molecular Medicine, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Egyetem ter 1, Debrecen, Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Doctoral School of Molecular Medicine, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Egyetem ter 1, Debrecen, Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Doctoral School of Molecular Medicine, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Egyetem ter 1, Debrecen, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, Department of Pulmonology, Semmelweis Hospital, of Borsod Abauj Zemplen County Central Hospital, and University Teaching Hospital Department of Pulmonology, Csabai Kapu 9-11, Miskolc, Department of Pulmonology, Semmelweis Hospital, of Borsod Abauj Zemplen County Central Hospital, and University Teaching Hospital Department of Pulmonology, Csabai Kapu 9-11, Miskolc, Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Doctoral School of Molecular Medicine, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Egyetem ter 1, Debrecen
Keywords:Human serum N-glycome, desialylation, capillary electrophoresis, lung diseases, molecular diagnostics,
malignant.
Abstract: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
applications.
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.
