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Updated: May 5, 2026
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Comprehensive proteogenomic characterization of rare kidney tumors
Ginny Xiaohe Li1, Lijun Chen2, Yi Hsiao3
1Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract:
Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.
Insights
This study identifies new biomarkers for diagnosing and understanding non-clear cell renal cell carcinomas (non-ccRCCs). These findings offer potential targets for better prognosis and treatment of kidney cancer subtypes.
Area of Science:
- Oncology
- Genomics
- Proteomics
- Metabolomics
Background:
- Non-clear cell renal cell carcinomas (non-ccRCCs) represent a heterogeneous group of kidney tumors requiring improved diagnostic and prognostic tools.
- Current clinical needs include refined differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and novel therapeutic targets.
- Understanding the molecular landscape of non-ccRCCs is crucial for advancing patient care.
Purpose of the Study:
- To perform multi-omics analyses on non-ccRCCs and compare them with clear cell renal cell carcinomas (ccRCCs).
- To identify proteogenomic, phosphorylation, glycosylation, and metabolic aberrations specific to RCC subtypes.
- To discover novel biomarkers for differential diagnosis and potential therapeutic targets in non-ccRCCs.
Main Methods:
- Multi-omics analyses (proteogenomics, phosphorylation, glycosylation, metabolism) were conducted on 48 non-ccRCCs and 103 ccRCCs.
- Integration of single-cell and bulk transcriptome data was used to predict cell-of-origin and clarify subtype-specific signatures.
- Biomarker expression was analyzed for differentiation between specific RCC subtypes.
Main Results:
- Proteogenomic, phosphorylation, glycosylation, and metabolic aberrations were identified across RCC subtypes.
- High genome instability in RCCs correlated with overexpression of IGF2BP3 and PYCR1.
- Specific biomarkers (MAPRE3, ADGRF5, GPNMB, PIGR, SOSTDC1) were found to differentiate between renal oncocytoma, chromophobe RCC, papillary RCC, and MTSCC.
Conclusions:
- This study elucidates diverse proteogenomic signatures within RCC subtypes.
- Novel biomarkers have been identified for the differential diagnosis of non-ccRCCs.
- The findings provide insights into potential therapeutic targets for non-ccRCCs, complementing existing immunotherapies.
