Comparative analysis of the human serum N-glycome in lung cancer, COPD and their comorbidity using capillary electrophoresis

Brigitta Mészáros, Gábor Járvás, Anna Farkas, Márton Szigeti, Zsuzsanna Kovács, Renáta Kun, Miklós Szabó, Eszter Csánky, András Guttman

Research output: Contribution to journalArticle

Abstract

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are prevalent ailments with a great challenge to distinguish them based on symptoms only. Since they require different treatments, it is important to find non-invasive methods capable to readily diagnose them. Moreover, COPD increases the risk of lung cancer development, leading to their comorbidity. In this pilot study the N-glycosylation profile of pooled human serum samples (90 patients each) from lung cancer, COPD and comorbidity (LC with COPD) patients were investigated in comparison to healthy individuals (control) by capillary gel electrophoresis with high sensitivity laser-induced fluorescence detection. Sample preparation was optimized for human serum samples introducing a new temperature adjusted denaturation protocol to prevent precipitation and increased endoglycosidase digestion time to assure complete removal of the N-linked carbohydrates. The reproducibility of the optimized method was <3.5%. Sixty-one N-glycan structures were identified in the pooled control human serum sample and the profile was compared to pooled lung cancer, COPD and comorbidity of COPD with lung cancer patient samples. One important finding was that no other sugar structures were detected in any of the patient groups, only quantitative differences were observed. Based on this comparative exercise, a panel of 13 N-glycan structures were identified as potential glycobiomarkers to reveal significant changes (>33% in relative peak areas) between the pathological and control samples. In addition to N-glycan profile changes, alterations in the individual N-glycan subclasses, such as total fucosylation, degree of sialylation and branching may also hold important glycobiomarker values.

Original languageEnglish
Article number121913
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1137
DOIs
Publication statusPublished - Jan 15 2020

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Capillary electrophoresis
Pulmonary diseases
Capillary Electrophoresis
Chronic Obstructive Pulmonary Disease
Comorbidity
Lung Neoplasms
Serum
Polysaccharides
Glycosylation
Denaturation
Glycoside Hydrolases
Electrophoresis
Digestion
Lasers
Fluorescence
Gels
Carbohydrates
Temperature
Therapeutics

Keywords

  • capillary electrophoresis
  • human serum
  • N-linked glycan
  • pulmonary diseases

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Comparative analysis of the human serum N-glycome in lung cancer, COPD and their comorbidity using capillary electrophoresis. / Mészáros, Brigitta; Járvás, Gábor; Farkas, Anna; Szigeti, Márton; Kovács, Zsuzsanna; Kun, Renáta; Szabó, Miklós; Csánky, Eszter; Guttman, András.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1137, 121913, 15.01.2020.

Research output: Contribution to journalArticle

Mészáros, Brigitta ; Járvás, Gábor ; Farkas, Anna ; Szigeti, Márton ; Kovács, Zsuzsanna ; Kun, Renáta ; Szabó, Miklós ; Csánky, Eszter ; Guttman, András. / Comparative analysis of the human serum N-glycome in lung cancer, COPD and their comorbidity using capillary electrophoresis. In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2020 ; Vol. 1137.
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AU - Farkas, Anna

AU - Szigeti, Márton

AU - Kovács, Zsuzsanna

AU - Kun, Renáta

AU - Szabó, Miklós

AU - Csánky, Eszter

AU - Guttman, András

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AB - Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are prevalent ailments with a great challenge to distinguish them based on symptoms only. Since they require different treatments, it is important to find non-invasive methods capable to readily diagnose them. Moreover, COPD increases the risk of lung cancer development, leading to their comorbidity. In this pilot study the N-glycosylation profile of pooled human serum samples (90 patients each) from lung cancer, COPD and comorbidity (LC with COPD) patients were investigated in comparison to healthy individuals (control) by capillary gel electrophoresis with high sensitivity laser-induced fluorescence detection. Sample preparation was optimized for human serum samples introducing a new temperature adjusted denaturation protocol to prevent precipitation and increased endoglycosidase digestion time to assure complete removal of the N-linked carbohydrates. The reproducibility of the optimized method was <3.5%. Sixty-one N-glycan structures were identified in the pooled control human serum sample and the profile was compared to pooled lung cancer, COPD and comorbidity of COPD with lung cancer patient samples. One important finding was that no other sugar structures were detected in any of the patient groups, only quantitative differences were observed. Based on this comparative exercise, a panel of 13 N-glycan structures were identified as potential glycobiomarkers to reveal significant changes (>33% in relative peak areas) between the pathological and control samples. In addition to N-glycan profile changes, alterations in the individual N-glycan subclasses, such as total fucosylation, degree of sialylation and branching may also hold important glycobiomarker values.

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