PhD Scientific Days 2023

Pharmaceutical Sciences I.

Exploring Proteomics and Glycosaminoglycan Profiles in ALK Rearranged Lung Tumor Samples

Text of the abstract

Introduction: Lung cancer is one of the most common types of cancer responsible for the most cancer-related deaths, therefore a detailed understanding of the molecular changes is of utmost importance.
Aims: In this study, we aimed to characterize the proteomic and glycosaminoglycan (GAG) composition of ALK rearranged lung tumor regions. Mapping the differences between the given tissue regions may give a better insight into the biological processes underlying tumor formation and progression.
Methods: A total of 22 regions on seven tissue sections were examined by nanoUHPLC-MS/MS measurements after tryptic, heparin lyase, and chondroitinase ABC digestion, respectively. Sample group comparisons based on morphological classification (e.g. solid, tubular, papillary tumor; adjacent normal) will be shown. Proteins were tested for expression differences and the biological function of differentially expressed proteins were visualized via protein interaction networks. Glycomic investigations were interpreted based on the total amount and sulfation patterns of chondroitin-sulfate (CS) and heparan-sulfate (HS) disaccharides. The differences between individual samples were examined using principal component analysis.
Results: Proteomic analysis revealed that differentially expressed proteins between different morphological tumor regions were mostly involved in regulating protein synthesis, while those between adjacent normal and different tumor regions took part in several other biological processes, e.g. extracellular matrix organization and protein folding.
Compared to adjacent normal tissue regions, all tumor sample groups showed increased CS and HS content and the mean sulfation also increased. The three tumor types showed the largest differences in the total amount of HS chains.
In both proteomic and GAG-omic principal component analysis, adjacent normal tissue regions were separated from tumor samples in all cases, while the different tumor types partially overlapped.
Conclusion: Our study provides an excellent starting point for further studies investigating larger number of ALK rearranged lung cancer patients, as well as for proteomic and GAG-omic characterization of other gene rearrangements.
Funding: National Research, Development, and Innovation Office of Hungary (FK 131603 and KNN121510) and János Bolyai Research Scholarship of the Hungarian Academy of Sciences.