Integrated Analysis of Three Publicly Available Gene Expression Profiles Identified Genes and Pathways Associated with Clear Cell Renal Cell Carcinoma.

Abstract

BackgroundAlthough advances have been achieved in the therapy of clear cell renal cell carcinoma (ccRCC), the pathogenesis of ccRCC is not yet fully understood. This study aimed to explore the critical genes and pathways associated with ccRCC by meta-analysis.Material/MethodsWe performed an integrated analysis of 3 publicly available microarray datasets developed from ccRCC tumor samples and normal tissues. A list of overlapped differentially expressed genes (DEGs) with the consistent expression trend in ccRCC tumor samples were identified, for which the protein–protein interaction (PPI) network was constructed, followed by topology structure and module analysis. The microRNA (miRNA) regulatory network and ccRCC associated pathway network were reconstructed.ResultsA total of 504 genes were found to be consistently and differentially regulated based on 3 microarray datasets. The overrepresented pathways for DEGs included citric acid cycle (TCA cycle) and peroxisome proliferator-activated receptor (PPAR) signaling pathway and cell cycle. The PPI network was clustered into 6 modules that were closely related with the M phase, desmosome assembly, and response to hormone stimulus. The hsa04110: cell cycle and hsa04510: focal adhesion were the significant pathways associated with ccRCC overlapped with enrichment analysis. KDR and ITGB4 were focal-adhesion-associated genes, which were regulated by has-miR-424 and has-miR-204, respectively. CCND2 and CCNA2 were cell-cycle-associated genes, which were regulated by hsa-miR-324-3p, hsa-miR-146a and hsa-miR-145.ConclusionsCell cycle and focal adhesion were dysregulated in ccRCC, which were associated with the expression of CCND2, ITGB4, KDR, and CCNA2 genes. The deregulation of pathways and associated genes may provide insights to ccRCC research and therapy.