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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
Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma
David J Clark1, Saravana M Dhanasekaran2, Francesca Petralia3
1Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA.
Abstract:
To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.
Insights
This study reveals distinct molecular subgroups in clear cell renal cell carcinoma (ccRCC) by integrating multi-omics data. Findings identify key protein dysregulations and immune subtypes, paving the way for targeted ccRCC treatments.
Area of Science:
- Oncology
- Genomics
- Proteomics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a complex malignancy.
- Understanding its molecular drivers is crucial for effective treatment strategies.
Purpose of the Study:
- To comprehensively characterize the molecular landscape of treatment-naive ccRCC.
- To identify deregulated functional modules and immune subtypes driving ccRCC pathobiology.
- To provide a basis for rational, pathobiology-informed treatment selection.
Main Methods:
- Multi-omics characterization (genomic, epigenomic, transcriptomic, proteomic, phosphoproteomic) of ccRCC and adjacent normal tissues.
- Proteogenomic integration to link genomic alterations with protein dysregulation.
- Identification of microenvironment cell signatures to define immune subtypes.
Main Results:
- A distinct molecular subgroup of ccRCC associated with genomic instability was identified.
- Proteogenomic analysis revealed dysregulation in oxidative phosphorylation, protein translation, and phospho-signaling pathways.
- Four distinct immune-based ccRCC subtypes were delineated based on microenvironment cell signatures.
Conclusions:
- This large-scale proteogenomic analysis provides deep insights into ccRCC pathobiology.
- The findings highlight the functional impact of genomic alterations on cellular mechanisms.
- The identified molecular and immune subtypes offer potential targets for precision medicine in ccRCC.
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