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

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Asfa S., Toy H. I., Arshinchi Bonab R., Chrousos G. P., Pavlopoulou A., Geronikolou S. A.

International Journal of Environmental Research and Public Health, vol.20, no.13, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 13
  • Publication Date: 2023
  • Doi Number: 10.3390/ijerph20136288
  • Journal Name: International Journal of Environmental Research and Public Health
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus, Agricultural & Environmental Science Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, EMBASE, Food Science & Technology Abstracts, Geobase, MEDLINE, Pollution Abstracts, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: anticancer drugs, bioinformatics, epigenetic regulation, Ewing sarcoma, gene expression, protein–protein interactions
  • Dokuz Eylül University Affiliated: Yes


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.