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Updated: Jun 13, 2026
The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
From Genes to Proteins: The Indispensable Role of Proteogenomics in Advancing Clear Cell Renal Cell Carcinoma
Filip Kasperczak1, Karolina Pawłowska-Kasperczak1, Antoni Szuścik1
1Department of Urology, J. Struś Hospital in Poznań, Szwajcarska 3, 61-285 Poznan, Poland.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is characterized by a complex molecular landscape driven by recurrent genetic alterations. While genomic and transcriptomic profiling have identified core drivers, they often fail to provide robust biomarkers due to the significant decoupling of mRNA and protein levels, as well as the critical role of post-translational modifications in tumor biology. This review synthesizes current evidence from landmark proteogenomic initiatives, such as the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and independent multi-omic studies. It evaluates the integration of genomic, transcriptomic, and proteomic data to map metabolic reprogramming, signalling pathway activity, and chromatin-level alterations in ccRCC. Proteogenomic analyses reveal that protein-level data provide a functional perspective that is missing from sequencing alone, specifically identifying suppressed oxidative phosphorylation, enhanced glycolysis, and the activation of the PI3K/AKT/mTOR cascade, independent of genetic mutations. Furthermore, proteogenomics has defined novel molecular subtypes and individual protein biomarkers, such as UCHL1 and p-mTOR, which correlate more accurately with clinical outcomes and therapeutic responses than their transcriptomic counterparts. Proteogenomics is a crucial tool for refining disease taxonomy and identifying novel therapeutic vulnerabilities in ccRCC. By bridging the gap between genotype and functional phenotype, this integrated approach facilitates more precise risk stratification and accelerates the development of personalized medicine through better-informed selection of targeted and immune-based therapies.
Insights
Proteogenomics integrates multi-omics data to reveal clear cell renal cell carcinoma (ccRCC) functional changes missed by genetics alone. This approach identifies new biomarkers and therapeutic targets for personalized ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Clear cell renal cell carcinoma (ccRCC) has a complex molecular profile driven by genetic changes.
- Genomic and transcriptomic data alone are insufficient for robust biomarker discovery due to mRNA-protein decoupling and post-translational modifications.
Purpose of the Study:
- To review and synthesize proteogenomic findings in ccRCC.
- To evaluate the integration of multi-omics data for understanding ccRCC biology and identifying biomarkers.
Main Methods:
- Synthesis of evidence from proteogenomic initiatives (e.g., CPTAC) and multi-omic studies.
- Integration of genomic, transcriptomic, and proteomic data analysis.
Main Results:
- Proteogenomics provides functional insights beyond sequencing, revealing metabolic reprogramming (suppressed oxidative phosphorylation, enhanced glycolysis) and activated signaling pathways (PI3K/AKT/mTOR).
- Novel ccRCC molecular subtypes and protein biomarkers (e.g., UCHL1, p-mTOR) with superior clinical correlation were identified.
- Protein-level data offer a more accurate reflection of tumor biology than transcriptomic data.
Conclusions:
- Proteogenomics is essential for refining ccRCC classification and discovering therapeutic vulnerabilities.
- This integrated approach bridges genotype and phenotype, enabling precise risk stratification and personalized medicine for ccRCC.
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