Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes

Lung cancer is among the most commonly diagnosed cancer types worldwide. Studying the molecular changes underlying lung cancer is crucial for understanding tumor formation and identifying new therapeutic targets and early markers of the disease to decrease mortality. Investigation of glycosaminoglyc...

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Main Authors: Domonkos Pál, Fanni Bugyi, Dávid Virág, Dániel Szabó, Gitta Schlosser, Ilona Kovalszky, Tünde Harkó, Judit Moldvay, Lilla Turiák
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666893925001641
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author Domonkos Pál
Fanni Bugyi
Dávid Virág
Dániel Szabó
Gitta Schlosser
Ilona Kovalszky
Tünde Harkó
Judit Moldvay
Lilla Turiák
author_facet Domonkos Pál
Fanni Bugyi
Dávid Virág
Dániel Szabó
Gitta Schlosser
Ilona Kovalszky
Tünde Harkó
Judit Moldvay
Lilla Turiák
author_sort Domonkos Pál
collection DOAJ
description Lung cancer is among the most commonly diagnosed cancer types worldwide. Studying the molecular changes underlying lung cancer is crucial for understanding tumor formation and identifying new therapeutic targets and early markers of the disease to decrease mortality. Investigation of glycosaminoglycan chains offer novel insights, as they play major roles in various signaling events in the tumor microenvironment. In this work we have determined the abundance and sulfation characteristics of chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans in human lung adenocarcinoma tissue sections. The cohort included samples with genetic alterations in key genes such as anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR) as well as triple wild type samples. CS/DS chains were cleaved using Chondroitinase ABC enzyme and the disaccharides were extracted from the tissue surface and analyzed using liquid chromatography-mass spectrometry. We identified significant changes in the relative abundance of the 4-O-sulfated CS disaccharide between samples with different genetic alterations and in the 6-O-/4-O-sulfation ratio between the ALK and EGFR group. This is the first study comparing CS/DS characteristics in lung adenocarcinoma samples with different genetic alterations and our findings suggest the importance of further testing to understand their role in tumor progression.
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spelling doaj-art-6c0e40fac8594af1a1901a96902c06be2025-08-20T03:45:10ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392025-06-011010082610.1016/j.carpta.2025.100826Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenesDomonkos Pál0Fanni Bugyi1Dávid Virág2Dániel Szabó3Gitta Schlosser4Ilona Kovalszky5Tünde Harkó6Judit Moldvay7Lilla Turiák8MTA-HUN-REN TTK Lendület (Momentum) Glycan Biomarker Research Group, HUN-REN Research Centre for Natural Sciences, H-1117, Magyar tudósok körútja 2., Budapest, Hungary; Semmelweis University, Doctoral School, 1085, Üllői út 26., Budapest, HungaryMTA-HUN-REN TTK Lendület (Momentum) Glycan Biomarker Research Group, HUN-REN Research Centre for Natural Sciences, H-1117, Magyar tudósok körútja 2., Budapest, HungaryMTA-HUN-REN TTK Lendület (Momentum) Glycan Biomarker Research Group, HUN-REN Research Centre for Natural Sciences, H-1117, Magyar tudósok körútja 2., Budapest, HungaryMS Proteomics Research Group, HUN-REN Research Centre for Natural Sciences, H-1117 Magyar tudósok körútja 2., Budapest, HungaryMTA-ELTE Lendület (Momentum) Ion Mobility Mass Spectrometry Research Group, ELTE Eötvös Loránd University, H-1117 Pázmány Péter sétány 1/A, Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, 1085, Üllői út 26., Budapest, HungaryNational Korányi Institute of Pulmonology, Korányi Frigyes út 1, Budapest, H-1121, HungaryNational Korányi Institute of Pulmonology, Korányi Frigyes út 1, Budapest, H-1121, Hungary; Pulmonology Clinic, Albert Szent-Györgyi Medical School, University of Szeged, Alkotmány u. 36., Deszk, H-6771, HungaryMTA-HUN-REN TTK Lendület (Momentum) Glycan Biomarker Research Group, HUN-REN Research Centre for Natural Sciences, H-1117, Magyar tudósok körútja 2., Budapest, Hungary; Corresponding author.Lung cancer is among the most commonly diagnosed cancer types worldwide. Studying the molecular changes underlying lung cancer is crucial for understanding tumor formation and identifying new therapeutic targets and early markers of the disease to decrease mortality. Investigation of glycosaminoglycan chains offer novel insights, as they play major roles in various signaling events in the tumor microenvironment. In this work we have determined the abundance and sulfation characteristics of chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans in human lung adenocarcinoma tissue sections. The cohort included samples with genetic alterations in key genes such as anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR) as well as triple wild type samples. CS/DS chains were cleaved using Chondroitinase ABC enzyme and the disaccharides were extracted from the tissue surface and analyzed using liquid chromatography-mass spectrometry. We identified significant changes in the relative abundance of the 4-O-sulfated CS disaccharide between samples with different genetic alterations and in the 6-O-/4-O-sulfation ratio between the ALK and EGFR group. This is the first study comparing CS/DS characteristics in lung adenocarcinoma samples with different genetic alterations and our findings suggest the importance of further testing to understand their role in tumor progression.http://www.sciencedirect.com/science/article/pii/S2666893925001641GlycosaminoglycanChondroitin/dermatan sulfateLung adenocarcinomaALKEGFRKRAS
spellingShingle Domonkos Pál
Fanni Bugyi
Dávid Virág
Dániel Szabó
Gitta Schlosser
Ilona Kovalszky
Tünde Harkó
Judit Moldvay
Lilla Turiák
Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes
Carbohydrate Polymer Technologies and Applications
Glycosaminoglycan
Chondroitin/dermatan sulfate
Lung adenocarcinoma
ALK
EGFR
KRAS
title Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes
title_full Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes
title_fullStr Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes
title_full_unstemmed Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes
title_short Analysis and characterization of chondroitin/dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in ALK, EGFR and KRAS oncogenes
title_sort analysis and characterization of chondroitin dermatan sulfate composition of lung adenocarcinoma tissues with different types of genetic alterations in alk egfr and kras oncogenes
topic Glycosaminoglycan
Chondroitin/dermatan sulfate
Lung adenocarcinoma
ALK
EGFR
KRAS
url http://www.sciencedirect.com/science/article/pii/S2666893925001641
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