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Updated: Nov 24, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
A pan-kidney cancer study identifies subtype specific perturbations on pathways with potential drivers in renal cell
Xiaohui Zhan1,2,3, Yusong Liu4,5, Christina Y Yu4,6
1National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518037, China. xhzhan@cqmu.edu.cn.
Background:
Renal cell carcinoma (RCC) is a complex disease and is comprised of several histological subtypes, the most frequent of which are clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (PRCC) and chromophobe renal cell carcinoma (ChRCC). While lots of studies have been performed to investigate the molecular characterizations of different subtypes of RCC, our knowledge regarding the underlying mechanisms are still incomplete. As molecular alterations are eventually reflected on the pathway level to execute certain biological functions, characterizing the pathway perturbations is crucial for understanding tumorigenesis and development of RCC.
Methods:
In this study, we investigated the pathway perturbations of various RCC subtype against normal tissue based on differential expressed genes within a certain pathway. We explored the potential upstream regulators of subtype-specific pathways with Ingenuity Pathway Analysis (IPA). We also evaluated the relationships between subtype-specific pathways and clinical outcome with survival analysis.
Results:
In this study, we carried out a pathway-based analysis to explore the mechanisms of various RCC subtypes with TCGA RNA-seq data. Both commonly altered pathways and subtype-specific pathways were detected. To identify the distinctive characteristics of each subtype, we focused on subtype-specific perturbed pathways. Specifically, we observed that some of the altered pathways were regulated by several recurrent upstream regulators which presenting different expression patterns among distinct RCC subtypes. We also noticed that a large number of perturbed pathways were controlled by the subtype-specific upstream regulators. Moreover, we also evaluated the relationships between perturbed pathways and clinical outcome. Prognostic pathways were identified and their roles in tumor development and progression were inferred.
Conclusions:
In summary, we evaluated the relationships among pathway perturbations, upstream regulators and clinical outcome for differential subtypes in RCC. We hypothesized that the alterations of common upstream regulators as well as subtype-specific upstream regulators work together to affect the downstream pathway perturbations and drive cancer initialization and prognosis. Our findings not only increase our understanding of the mechanisms of various RCC subtypes, but also provide targets for personalized therapeutic intervention.
Insights
Investigating pathway alterations in renal cell carcinoma (RCC) subtypes reveals key upstream regulators driving cancer development and prognosis. These findings offer potential targets for personalized RCC therapies.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Renal cell carcinoma (RCC) encompasses diverse histological subtypes, including clear cell (ccRCC), papillary (PRCC), and chromophobe (ChRCC).
- Despite extensive research, the precise molecular mechanisms underlying RCC tumorigenesis and progression remain incompletely understood.
- Pathway-level analysis is critical for deciphering the functional consequences of molecular alterations in RCC development.
Purpose of the Study:
- To investigate pathway perturbations across different RCC subtypes compared to normal kidney tissue.
- To identify subtype-specific pathways and their upstream regulators.
- To explore the correlation between pathway alterations and clinical outcomes in RCC patients.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) RNA-seq data for pathway-based analysis of RCC subtypes.
- Employed Ingenuity Pathway Analysis (IPA) to identify upstream regulators of differentially expressed genes within pathways.
- Conducted survival analysis to assess the relationship between pathway perturbations and patient prognosis.
Main Results:
- Identified both commonly altered and subtype-specific perturbed pathways across RCC subtypes.
- Discovered recurrent upstream regulators with distinct expression patterns influencing subtype-specific pathways.
- Found that a significant number of perturbed pathways are regulated by subtype-specific upstream regulators.
- Established links between specific perturbed pathways and clinical outcomes, identifying prognostic pathways.
Conclusions:
- Pathway perturbations, driven by common and subtype-specific upstream regulators, collectively influence RCC initiation and prognosis.
- The study enhances understanding of RCC subtype mechanisms.
- Identified potential therapeutic targets for personalized interventions in RCC treatment.
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