PhD Scientific Days 2025

Poster Session III. - P: Health Sciences

Investigation of Glycosaminoglycans in Lung Cancer

Name of the presenter

Domonkos Pál

Institute/workplace of the presenter

HUN-REN Research Centre for Natural Sciences

Authors

Domonkos Pál^1,2, Lilla Turiák¹

1: HUN-REN Research Centre for Natural Sciences
2: Semmelweis University

Text of the abstract

Introduction
Lung cancer is globally the second most frequently diagnosed cancer, with the highest mortality rate. Carbohydrates are utilized as diagnostic biomarkers in various diseases including cancer. During tumor progression, glycosaminoglycans (GAGs) undergo changes in their abundance and structure.

Aims
Our aim was to conduct a comprehensive quantitative and qualitative glycomic study of chondroitin sulfate (CS) and heparan sulfate (HS) GAG disaccharides in case of small cell lung cancer and different non-small cell lung cancer tissue subtypes, analyzing both tumor and tumor-adjacent regions. Our further objective was to investigate CS disaccharides in lung adenocarcinoma (AC) human tissues harboring different genetic alterations (EGFR, KRAS, ALK) and wild-type, WT.

Methods
The GAG chains were enzymatically digested on the surface of tissue sections. The CS and HS disaccharides were extracted and purified. Their analysis was performed by HPLC-MS on self-packed capillary columns with hydrophilic interaction liquid chromatography and weak anion exchange combined solid phase using ammonium formate salt gradients. The chromatographic peak areas of the investigated disaccharides were analyzed. Statistical tests and data visualization were performed in R and Python.

Results
In the different lung phenotypes, the abundance of CS was doubled in tumor regions, while in the case of HS it did not show significant changes. The average degree of sulfation significantly increased in all examined tumor phenotypes compared to tumor-adjacent normal regions. In AC samples, the 6-O-/4-O-sulfation ratio of CS was increased as opposed to other lung tumor phenotypes. O-sulfated HS components were elevated in the tumor samples. Between the different genetic alterations of lung AC, the relative abundance of the 4-O-sulfated D0a4 disaccharide was significantly lower in the EGFR group compared to the ALK and WT groups.
 
Conclusion
The glycomic analysis uncovered distinct GAG sulfation patterns among different lung cancer subtypes and genetic alterations, advancing diagnostic and molecular insights.

Funding
Funding from the National Research, Development and Innovation Office (OTKA FK131603) is acknowledged.

E-mail: pal.domonkos@phd.semmelweis.hu
Institute: HUN-REN RCNS
Supervisor: Dr. Lilla Turiák