PhD Scientific Days 2023

Translational Medicine I.

Analysis of the Glycosylation Pattern and Concentration of Alpha-1-acid Glycoprotein as a New Biomarker in Malignant Melanoma

Text of the abstract

Introduction: Malignant melanoma (MM) is a pigmented skin tumor with high metastatic potential and increasing incidence. There is a need for diagnostic biomarkers for early tumor detection. S100 serum protein is useful for follow-up and for monitoring the progression in high-risk melanoma patient, but its specificity and sensitivity is insufficient in the early stages. Up to now, no serum biomarker with relevant diagnostic value has been identified. We investigated alpha-1-acid glycoprotein (AGP), as a potential new biomarker in MM. AGP is a highly glycosylated serum acute-phase protein produced primarily by the liver. In different pathological conditions, AGP can be released from extrahepatic tissues including cancer cells. In these conditions changes in its serum concentration and structure can occur.
Aims: To investigate changes in the glycosylation pattern and concentration of AGP in dermatological pathologies and to evaluate their diagnostic value as biomarkers.
Methods: Serum AGP of 18 high-risk MM patients and 19 healthy individuals as controls were isolated. After purification and enzymatic digestion, oligosaccharide side chains were subjected to anthranilic acid derivatization. Hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was used to determine the structure and amount of the glycans. Statistical evaluation of the glycosylation pattern of the samples was performed by linear discriminant analysis (LDA). We also examined the variation of AGP concentration in serum samples from patients with MM.
Results: More than 100 different glycan isomers were identified. Based on the results, it can be concluded that the glycosylation pattern of AGP in MM undergoes significant changes. These changes appear as the accumulation of side chains containing more sialic acid, fucose units, and more branching. The concentration of AGP in MM patients were increased in higher-stage tumors compared to literature data (1 g/l), but no significant correlation were detected between the stages and increased concentration.
Conclusion: These findings suggest that the glycosylation pattern of AGP may serve as a more sensitive and specific biomarker than currently available in MM.
Funding: LG was supported by the New National Excellence Program of the Ministry of Human Capacities (ÚNKP-22-2-III-SE-55); EFOP-3.6.3-VEKOP-16-2017-00009