Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach

Seyedehsadaf Asfa, Halil Ibrahim Toy, Reza Arshinchi Bonab, George P. Chrousos, Athanasia Pavlopoulou () and Styliani A. Geronikolou ()
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Seyedehsadaf Asfa: Izmir Biomedicine and Genome Center (IBG), 35340 Izmir, Turkey
Halil Ibrahim Toy: Izmir Biomedicine and Genome Center (IBG), 35340 Izmir, Turkey
Reza Arshinchi Bonab: Izmir Biomedicine and Genome Center (IBG), 35340 Izmir, Turkey
George P. Chrousos: Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, Soranou Ephessiou 4, 11527 Athens, Greece
Athanasia Pavlopoulou: Izmir Biomedicine and Genome Center (IBG), 35340 Izmir, Turkey
Styliani A. Geronikolou: Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, Soranou Ephessiou 4, 11527 Athens, Greece

IJERPH, 2023, vol. 20, issue 13, 1-17

Abstract: Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein–protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.

Keywords: Ewing sarcoma; anticancer drugs; bioinformatics; gene expression; epigenetic regulation; protein–protein interactions (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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