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

• Investigation of the CS/DS composition of LUAD tissue samples with different genetic alterations • On surface Chondroitinase ABC digestion and HPLC-MS analysis of CS/DS disaccharides • The relative amount of the D0a4 CS/DS disaccharide showed significant difference between the ALK-EGFR and WT-EGFR groups. • The 6-O-/4-O- sulfation ratio was significantly different between the ALK and EGFR sample groups. • The different mutation types within the EGFR sample group did not show any separation in terms of CS/DS disaccharide abundance 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.