Identification of target genes of cediranib in alveolar soft part sarcoma using a gene microarray

Abstract

The aim of the present study was to identify the target genes of cediranib and the associated signaling pathways in alveolar soft part sarcoma (ASPS). A microarray dataset (GSE32569) was obtained from the Gene Expression Omnibus database. The R software package was used for data normalization and screening of differentially expressed genes (DEGs). The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology analysis. Gene Set Enrichment Analysis was performed to obtain the up- and downregulated pathways in ASPS. The Distant Regulatory Elements of co-regulated genes database was used to identify the transcription factors (TFs) that were enriched in the signaling pathways. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and was visualized using Cytoscape software. A total of 71 DEGs, including 59 upregulated genes and 12 downregulated genes, were identified. Gene sets associated with ASPS were enriched primarily in four signaling pathways: The phenylalanine metabolism pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the taste transduction pathway and the intestinal immune network for the production of immunoglobulin A. Furthermore, 107 TFs were identified to be enriched in the MAPK signaling pathway. Certain genes, including those coding for Fms-like tyrosine kinase 1, kinase insert domain receptor, E-selectin and platelet-derived growth factor receptor D, that were associated with other genes in the PPI network, were identified. The present study identified certain potential target genes and the associated signaling pathways of cediranib action in ASPS, which may be helpful in understanding the efficacy of cediranib and the development of new targets for cediranib.

Keywords: Gene Set Enrichment Analysis; alveolar soft part sarcoma; differentially expressed genes; protein-protein interaction network.

Figure 1.

Microarray data normalization and heat-map of DEGs. Microarray data, (A) prior to normalization and (B) following normalization. Red represents pre-treatment with cediranib and blue represents post-treatment with cediranib, for between 3 and 5 days. (C) Hierarchical clustering analysis heat-map of DEGs. Red represents downregulated genes and blue represents upregulated genes. DEG, differentially expressed gene.

Figure 2.

Enrichment scores of the MAPK signaling pathway. ‘Case’ represents the case groups. ‘Control’ represents the control groups. KEGG, Kyoto Encyclopedia of Genes and Genomes; MAPK, mitogen-activated protein kinase.

Figure 3.

Protein-protein interaction network of DEGs. Spheres represent DEGs and lines represent direct interactions between DEGs. DEG, differentially expressed gene.