Revealing the role of VEGFA in clear cell sarcoma of the kidney by protein-protein interaction network and significant pathway analysis

Despite clear cell sarcoma of the kidney (CCSK) being the second most common renal tumor in children, its mechanism has not yet been fully investigated. The aim of the present study was to investigate the potential role of vascular endothelial growth factor A (VEGFA) in CCSK development. Following preprocessing of the original GSE2712 data, the differentially-expressed genes (DEGs) between 14 CCSK and 3 fetal kidney samples were identified through Significance Analysis of Microarrays, using the R package. Pathway enrichment analysis was then performed on the DEGs. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and the DEGs that were enriched in the most significant pathways. Following this, gene ontology analysis was performed on the VEGFA-associated genes, whilst transcription factor binding site analysis was conducted on the hot genes. A total of 2,681 DEGs, including 543 upregulated and 2,138 downregulated genes, were identified, and these were significantly enriched in pathways associated with cancer and focal adhesion. Furthermore, VEGFA, integrin β1, integrin αV, v-akt murine thymoma viral oncogene homolog 1 and endothelial growth factor receptor were identified as hot genes in the PPI network. In addition, the upregulated VEGFA-associated genes, cyclin D1 and cyclin-dependent kinase inhibitor 1B, affected kinase regulation, and the downregulated VEGFA-associated genes, receptor tyrosine-protein kinase erbB-2, mesenchymal-epithelial transition tyrosine kinase receptor and kinase insert domain receptor, were enriched in the protein tyrosine kinase process. It was identified that VEGFA was regulated by restorer of fertility, erythromycin resistance methylase, GA binding protein subunit α, norepinephrine transporter, nuclear factor κB and Sp2 transcription factor genes. Overall, VEGFA and its associated genes serve important roles during CCSK development, and alongside transcription factors, they may function as novel therapeutic targets for disease treatment.