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Updated: Dec 13, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Integrated Analysis of Three Publicly Available Gene Expression Profiles Identified Genes and Pathways Associated
YuPing Han1, LinLin Wang2, Ye Wang3
1Department of Urology, The Third Hospital of Jilin University, Changchun, Jilin, China (mainland).
Abstract:
BACKGROUND Although 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 AND METHODS We 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. RESULTS A 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. CONCLUSIONS Cell 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.
Insights
This meta-analysis identified key genes and pathways in clear cell renal cell carcinoma (ccRCC). Cell cycle and focal adhesion pathways are significantly dysregulated, offering new therapeutic targets for ccRCC.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Clear cell renal cell carcinoma (ccRCC) therapy advances, yet its pathogenesis remains unclear.
- Understanding ccRCC molecular mechanisms is crucial for improved treatment strategies.
Purpose of the Study:
- To identify critical genes and pathways implicated in ccRCC pathogenesis using meta-analysis.
- To explore potential molecular targets for ccRCC research and therapy.
Main Methods:
- Integrated analysis of three public microarray datasets from ccRCC tumor and normal tissues.
- Identification of consistently differentially expressed genes (DEGs) and construction of protein-protein interaction (PPI) and miRNA regulatory networks.
- Pathway enrichment analysis and module identification within the PPI network.
Main Results:
- 504 consistently differentially regulated genes were identified in ccRCC.
- Key pathways implicated include the citric acid cycle (TCA cycle), PPAR signaling, and cell cycle.
- Cell cycle and focal adhesion pathways were significantly associated with ccRCC, involving genes like KDR, ITGB4, CCND2, and CCNA2, regulated by specific miRNAs.
Conclusions:
- Cell cycle and focal adhesion pathways are demonstrably dysregulated in ccRCC.
- Specific genes (CCND2, ITGB4, KDR, CCNA2) and their miRNA regulators are critical in ccRCC.
- These findings provide novel insights for ccRCC research and therapeutic development.
