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Modeling of the Desialylated Human Serum N-glycome for Molecular Diagnostic Applications in Inflammatory and Malignant lung Diseases

Author(s):

Anna Farkas*, Brigitta Mészáros, Máté Szarka, Márton Szigeti, János Kappelmayer, Miklós Szabó, Eszter Csánky and András Guttman   Pages 1 - 8 ( 8 )

Abstract:


Background: Immunoglobulin G and A, transferrin, haptoglobin and alpha-1-antitrypsin are representing approximately 85% of the human serum glycoproteome and their N-glycosylation analysis may lead to discover 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, in medium extent for COPD and in lesser extent for comorbidity. Also, some increase of the afucosylated-galactosylatedbiantennary 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 N-glycome holds glycoprotein specific molecular diagnostic potential for malignant and inflammatory lung diseases, which can be modeled with the five-protein mixture.

Keywords:

Human serum N-glycome, desialylation, capillary electrophoresis, lung diseases, molecular diagnostics

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



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