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Authors Liao H, Xie X, Xu Y, Huang G
Received 25 April 2018
Accepted for publication 3 August 2018
Published 15 October 2018 Volume 2018:11 Pages 6947—6956
DOI https://doi.org/10.2147/OTT.S172190
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr Carlos E Vigil
Background: The aim of this study was to identify the driver genes associated with
chemotherapy resistance of Ewing’s sarcoma and potential targets for Ewing’s
sarcoma treatment.
Methods: Two mRNA microarray datasets, GSE12102 and GSE17679, were
downloaded from the Gene Expression Omnibus database, which contain 94 human
Ewing’s sarcoma samples, including 65 from those who experienced a relapse and
29 from those with no evidence of disease. The differentially expressed genes
(DEGs) were identified using LIMMA package R. Subsequently, Gene Ontology and
Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were
performed for DEGs using Database for Annotation, Visualization and Integrated
Analysis. The protein–protein interaction network was constructed using
Cytoscape software, and module analysis was performed using Molecular Complex Detection.
Results: A total of 206 upregulated DEGs and 141 downregulated DEGs were
identified. Upregulated DEGs were primarily enriched in DNA replication,
nucleoplasm and protein kinase binding for biological processes, cellular
component and molecular functions, respectively. Downregulated DEGs were
predominantly involved in receptor clustering, membrane raft, and
ligand-dependent nuclear receptor binding. The protein–protein interaction
network of DEGs consisted of 150 nodes and 304 interactions. Thirteen hub genes
were identified, and biological analysis revealed that these genes were
primarily enriched in cell division, cell cycle, and mitosis. Furthermore,
based on closeness centrality, betweenness centrality, and degree centrality,
the three most significant genes were identified as GAPDH , AURKA , and EHMT2 . Furthermore, the
significant network module was composed of nine genes. These genes were
primarily enriched in mitotic nuclear division, mitotic chromosome
condensation, and nucleoplasm.
Conclusion: These hub genes, especially GAPDH , AURKA , and EHMT2 , may be closely associated
with the progression of Ewing’s sarcoma chemotherapy resistance, and further
experiments are needed for confirmation.
Keywords: Ewing’s sarcoma, chemotherapy resistance, differentially expressed
gene, enrichment analysis, network