Abstract

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. The study aimed to identify genetic characteristics and reveal the underlying mechanisms in RCC. GSE53757, GSE46699, and TCGA KIRC database (n = 897) were analyzed to screen differentially expressed genes (DEGs) in RCC. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, followed by the analysis of the protein-protein interaction (PPI) network of the DEGs by Cytoscape software. In all, 834 DEGs were identified in RCC, including 416 upregulated genes and 418 downregulated genes. The top 10 hub genes, VEGFA, EGFR, EGF, CD44, CD86, FN1, ITGAM, ITGB2, TLR2, and PTPRC, were identified from the PPI network according to the core degree. The following subnetwork revealed that these significant modules were enriched in positive regulation of response to external stimulus, regulation of leukocyte-mediated immunity, and regulation of exocytosis. The expressions of these hub genes were also validated using qRT-PCR and IHC in Changzheng RCC database (n = 160). We especially found that half of the top ten hub genes were cell adhesion-related molecules, which were associated with RCC progression and poor prognosis. In conclusion, these hub genes, particularly cell adhesion-related molecules, could be used as prognostic biomarkers and potential therapeutic targets for RCC.

Highlights

  • Renal cell carcinoma (RCC) is the third-leading cause of death among urological tumors, and the estimated numbers of new RCC cases and deaths are 62,700 and 14,240, respectively, in the USA for 2016 [1]. e incidence of RCC has been rising for over two decades [2]. e localized RCC and metastatic RCC fairly differ in consideration of prognosis and therapeutic approach. e 5-year cancer-specific survival is more than 70% in nonmetastatic RCC but dramatically decreases to less than 27.1% in metastatic RCC [3]

  • Our study found that epidermal growth factor receptor (EGFR)-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR mediated mRNA stability of EGFR [24]

  • We identified a number of key genes and pathways associated with RCC initiation and progression through a comprehensive bioinformatics analysis of differentially expressed genes (DEGs)

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Summary

Introduction

Renal cell carcinoma (RCC) is the third-leading cause of death among urological tumors, and the estimated numbers of new RCC cases and deaths are 62,700 and 14,240, respectively, in the USA for 2016 [1]. e incidence of RCC has been rising for over two decades [2]. e localized RCC and metastatic RCC fairly differ in consideration of prognosis and therapeutic approach. e 5-year cancer-specific survival is more than 70% in nonmetastatic RCC but dramatically decreases to less than 27.1% in metastatic RCC [3]. By gene expression profiling analysis on RCC, BioMed Research International some research has found many differentially expressed genes (DEGs) involved in crucial signaling pathways or biological processes. Several studies have identified some key genes and signaling pathways in kidney cancer by biological information analysis [10, 11]. Eckel-Passow et al found two key cancerpromoting genes, ANKS1B and ENRAGE, using 130 renal cancer and adjacent tissue expression profiling arrays [13]. Based on the original data from GEO online database, we identified the differentially expressed genes (DEGs) and key molecular pathways and constructed a regulatory network. Ese hub genes could be used as potential biomarkers and therapeutic targets They may bring a novel insight into renal cancer pathogenesis

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