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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Temporal Identification of Dysregulated Genes and Pathways in Clear Cell Renal Cell Carcinoma Based on Systematic
Shao-Mei Wang1, Ze-Qiang Sun2, Hong-Yun Li2
1Center for Kidney Disease, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.
Objective:
The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks.
Methods:
Firstly, normal and ccRCC PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, we identified altered modules using maximum weight bipartite matching and ranked them in nonincreasing order. Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test.
Results:
We obtained 136, 576, 693, and 531 disrupted modules of ccRCC stages I, II, III, and IV, respectively. Gene composition analyses of altered modules revealed that there were 56 common genes (such as MAPK1, CCNA2, and GSTM3) existing in the four stages. Besides pathway enrichment analysis identified 5 common pathways (glutathione metabolism, cell cycle, alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, and metabolism of xenobiotics by cytochrome P450) across stages I, II, III, and IV.
Conclusions:
We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC.
Insights
This study identifies key genes and metabolic pathways dysregulated in clear cell renal cell carcinoma (ccRCC) across all stages. These findings offer potential biomarkers for ccRCC diagnosis and therapeutic strategies.
Area of Science:
- Genomics
- Systems Biology
- Oncology
Background:
- Clear cell renal cell carcinoma (ccRCC) is a significant health concern.
- Understanding temporal gene and pathway dysregulation is crucial for effective treatment.
Purpose of the Study:
- To identify dysregulated genes and pathways in ccRCC over time.
- To analyze temporal changes in reweighted Protein-Protein Interaction (PPI) networks.
Main Methods:
- Inferred and reweighted normal and ccRCC PPI networks using Pearson correlation coefficient (PCC).
- Identified and ranked altered modules via maximum weight bipartite matching.
- Analyzed gene composition and performed pathway enrichment using the Expression Analysis Systematic Explored (EASE) test.
Main Results:
- Identified 136 to 693 disrupted modules across ccRCC stages I-IV.
- Found 56 common dysregulated genes (e.g., MAPK1, CCNA2, GSTM3) across all stages.
- Revealed 5 common dysregulated pathways including glutathione metabolism and cell cycle.
Conclusions:
- Successfully identified stage-specific and common dysregulated genes and pathways in ccRCC.
- These findings may serve as potential biomarkers for ccRCC.
- Identified processes could inform treatment strategies and elucidate ccRCC etiology.
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