Identification of hub genes associated with outcome of clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumor types of the urinary system. Bioinformatics tools have been used to identify new biomarkers of ccRCC and to explore the mechanisms underlying development and progression of ccRCC. The present study analyzed the differentially expressed genes (DEGs) associated with RCC using data obtained from Gene Expression Omnibus datasets and GEO2R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of these DEGs was performed and analyzed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes to identify the hub genes, defined as the genes with the highest degree of interrelation. Subsequently, differential expression and survival analyses of hub genes was performed using The Cancer Genome Atlas database and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Using GEO2R, 1,650 DEGs were identified, including 743 upregulated and 907 downregulated genes. GO and KEGG pathway analyses indicated that the upregulated DEGs were primarily involved in blood vessel and vasculature development, whereas downregulated DEGs were primarily involved in organic acid metabolic processes and carboxylic acid metabolic processes. Subsequently, important modules were identified in the PPI network using Cytoscape's Molecular Complex Detection. The 15 most connected hub genes were identified among DEGs, including glycine decarboxylase (GLDC), enolase 2 (ENO2) and topoisomerase II alpha. GEPIA revealed the association between expression levels of hub genes and survival. Specifically, GLDC and ENO2 were associated with the prognosis of patients with RCC and thus, the effects of GLDC and ENO2 involvement in renal cancer were investigated in vitro. GLDC and ENO2 affected the proliferation and apoptosis of renal cancer cells. These hub genes may reveal a new mechanism underlying development or progression of RCC and identify new markers for its diagnosis and prognosis.