Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma
A high-resolution HILIC-MS/MS method was developed to analyze anthranilic acid derivatives of <i>N</i>-glycans released from human serum alpha-1-acid glycoprotein (AGP). The method was applied to samples obtained from 18 patients suffering from high-risk malignant melanoma as well as 19...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/19/6003 |
| _version_ | 1827680587965530112 |
|---|---|
| author | Dávid Virág Tibor Kremmer Kende Lőrincz Norbert Kiss Antal Jobbágy Szabolcs Bozsányi Lili Gulyás Norbert Wikonkál Gitta Schlosser Adina Borbély Zsófia Huba Borbála Dalmadi Kiss István Antal Krisztina Ludányi |
| author_facet | Dávid Virág Tibor Kremmer Kende Lőrincz Norbert Kiss Antal Jobbágy Szabolcs Bozsányi Lili Gulyás Norbert Wikonkál Gitta Schlosser Adina Borbély Zsófia Huba Borbála Dalmadi Kiss István Antal Krisztina Ludányi |
| author_sort | Dávid Virág |
| collection | DOAJ |
| description | A high-resolution HILIC-MS/MS method was developed to analyze anthranilic acid derivatives of <i>N</i>-glycans released from human serum alpha-1-acid glycoprotein (AGP). The method was applied to samples obtained from 18 patients suffering from high-risk malignant melanoma as well as 19 healthy individuals. It enabled the identification of 102 glycan isomers separating isomers that differ only in sialic acid linkage (α-2,3, α-2,6) or in fucose positions (core, antenna). Comparative assessment of the samples revealed that upregulation of certain fucosylated glycans and downregulation of their nonfucosylated counterparts occurred in cancer patients. An increased ratio of isomers with more α-2,6-linked sialic acids was also observed. Linear discriminant analysis (LDA) combining 10 variables with the highest discriminatory power was employed to categorize the samples based on their glycosylation pattern. The performance of the method was tested by cross-validation, resulting in an overall classification success rate of 96.7%. The approach presented here is significantly superior to serological marker S100B protein in terms of sensitivity and negative predictive power in the population studied. Therefore, it may effectively support the diagnosis of malignant melanoma as a biomarker. |
| first_indexed | 2024-03-10T06:53:45Z |
| format | Article |
| id | doaj.art-17a20330ee6c4b21bfbab4d3a0fe5f3c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T06:53:45Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-17a20330ee6c4b21bfbab4d3a0fe5f3c2023-11-22T16:35:53ZengMDPI AGMolecules1420-30492021-10-012619600310.3390/molecules26196003Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant MelanomaDávid Virág0Tibor Kremmer1Kende Lőrincz2Norbert Kiss3Antal Jobbágy4Szabolcs Bozsányi5Lili Gulyás6Norbert Wikonkál7Gitta Schlosser8Adina Borbély9Zsófia Huba10Borbála Dalmadi Kiss11István Antal12Krisztina Ludányi13Department of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7., H-1092 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7., H-1092 Budapest, HungaryDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41., H-1085 Budapest, HungaryDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41., H-1085 Budapest, HungaryDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41., H-1085 Budapest, HungaryDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41., H-1085 Budapest, HungaryDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41., H-1085 Budapest, HungaryDepartment of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41., H-1085 Budapest, HungaryMTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, H-1117 Budapest, HungaryMTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, H-1117 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7., H-1092 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7., H-1092 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7., H-1092 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7., H-1092 Budapest, HungaryA high-resolution HILIC-MS/MS method was developed to analyze anthranilic acid derivatives of <i>N</i>-glycans released from human serum alpha-1-acid glycoprotein (AGP). The method was applied to samples obtained from 18 patients suffering from high-risk malignant melanoma as well as 19 healthy individuals. It enabled the identification of 102 glycan isomers separating isomers that differ only in sialic acid linkage (α-2,3, α-2,6) or in fucose positions (core, antenna). Comparative assessment of the samples revealed that upregulation of certain fucosylated glycans and downregulation of their nonfucosylated counterparts occurred in cancer patients. An increased ratio of isomers with more α-2,6-linked sialic acids was also observed. Linear discriminant analysis (LDA) combining 10 variables with the highest discriminatory power was employed to categorize the samples based on their glycosylation pattern. The performance of the method was tested by cross-validation, resulting in an overall classification success rate of 96.7%. The approach presented here is significantly superior to serological marker S100B protein in terms of sensitivity and negative predictive power in the population studied. Therefore, it may effectively support the diagnosis of malignant melanoma as a biomarker.https://www.mdpi.com/1420-3049/26/19/6003alpha-1-acid glycoproteinbiomarkerglycosylationhydrophilic interaction chromatographylinear discriminant analysismass spectrometry |
| spellingShingle | Dávid Virág Tibor Kremmer Kende Lőrincz Norbert Kiss Antal Jobbágy Szabolcs Bozsányi Lili Gulyás Norbert Wikonkál Gitta Schlosser Adina Borbély Zsófia Huba Borbála Dalmadi Kiss István Antal Krisztina Ludányi Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma Molecules alpha-1-acid glycoprotein biomarker glycosylation hydrophilic interaction chromatography linear discriminant analysis mass spectrometry |
| title | Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma |
| title_full | Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma |
| title_fullStr | Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma |
| title_full_unstemmed | Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma |
| title_short | Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma |
| title_sort | altered glycosylation of human alpha 1 acid glycoprotein as a biomarker for malignant melanoma |
| topic | alpha-1-acid glycoprotein biomarker glycosylation hydrophilic interaction chromatography linear discriminant analysis mass spectrometry |
| url | https://www.mdpi.com/1420-3049/26/19/6003 |
| work_keys_str_mv | AT davidvirag alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT tiborkremmer alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT kendelorincz alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT norbertkiss alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT antaljobbagy alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT szabolcsbozsanyi alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT liligulyas alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT norbertwikonkal alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT gittaschlosser alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT adinaborbely alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT zsofiahuba alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT borbaladalmadikiss alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT istvanantal alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma AT krisztinaludanyi alteredglycosylationofhumanalpha1acidglycoproteinasabiomarkerformalignantmelanoma |