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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
mRNA expression, tumor heterogeneity, and response to therapy in patients with advanced renal cell carcinoma treated
Cristina Aguzzi1, Simona De Summa2, Javier Molina-Cerrillo3
1School of Pharmacy, University of Camerino, Camerino, Macerata, Italy.
Background:
Renal Cell Carcinoma (RCC) represents a spectrum of tumors, characterized by heterogeneous growth patterns, histology and response to immune-based combinations.
Objectives:
The aim of the present retrospective analysis was to investigate the mRNA expression of 32 genes associated with RCC carcinogenesis and their potential involvement in patients treated with first-line immune-based combination therapies. Additionally, we examined the role of tumor heterogeneity by comparing mRNA expression levels between primary renal tumors and metastatic sites in a group of patients included in the ARON-1 study.
Patients And Methods:
The study included patients with advanced RCC treated with first-line immune-based therapies. Total RNA was extracted from fixed paraffin-embedded tissue slices using the RNeasy FFPE Mini Kit. Quantitative RT-PCR was performed using the IQ5 Multicolor real-time PCR detection system. Coefficient of variations were calculated for each gene and compared between primary and metastatic samples.
Results:
17 patients were included in this analysis; 9 of them had both primary and metastatic samples available. Three of the 4 patients showing the highest mRNA expression levels of the 32 analyzed genes reported complete remissions, while 2 of the 3 patients with the lowest expression levels were primary refractory to first-line therapy. As for tumor heterogeneity, VEGFA was the only gene significantly deregulated in the paired comparison.
Conclusions:
We showed differences in mRNA expression between primary and metastatic sites, and proposed a possible link to the response to first-line immune combination therapies. Additional research is required to clarify their potential as prognostic or predictive biomarkers.
Insights
Investigating 32 gene mRNA expression in advanced renal cell carcinoma (RCC) revealed potential links to immune therapy response. Tumor heterogeneity, particularly VEGFA deregulation, was observed between primary and metastatic sites.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Renal Cell Carcinoma (RCC) is a complex cancer with diverse characteristics and varied responses to immune-based treatments.
- Understanding the molecular underpinnings of RCC is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the mRNA expression of 32 genes linked to RCC carcinogenesis.
- To explore the potential role of these genes in patients receiving first-line immune-based combination therapies.
- To assess tumor heterogeneity by comparing gene expression between primary and metastatic RCC sites.
Main Methods:
- Retrospective analysis of 17 advanced RCC patients treated with first-line immune-based therapies.
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) to analyze mRNA expression of 32 genes.
- Comparison of mRNA expression levels between primary tumors and metastatic sites.
Main Results:
- Higher mRNA expression of the analyzed genes correlated with better response to immune therapy.
- Lower mRNA expression was associated with primary refractoriness to first-line therapy.
- VEGFA was the only gene significantly deregulated when comparing primary and metastatic RCC samples, indicating tumor heterogeneity.
Conclusions:
- Differences in mRNA expression exist between primary and metastatic RCC sites.
- Gene expression patterns may be linked to treatment response in advanced RCC.
- Further research is needed to validate these genes as prognostic or predictive biomarkers for RCC.
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