Related Experiment Video
Updated: Jun 10, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma
Matilda Roos-Mattila1,2,3, Pauliina Kallio4,5, Tamara J Luck5,6
1Department of Surgery, Helsinki University Hospital, Helsinki, Finland. matilda.roos-mattila@helsinki.fi.
Abstract:
Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far. We recruited five PM-ccRCC patients and investigated the genomic, single-cell transcriptomic, and drug sensitivity profiles of their patient-derived cells (PDCs). The PM depicted both expected and novel genomic alterations. Further, the transcriptomics differed from both primary and metastatic ccRCC, with upregulations of the PI3K/mTOR and - supporting the clinical observations - angiogenesis pathways. Data integration at pathway level showed that transcriptomics explained drug sensitivities the best. Accordingly, PM-ccRCC PDCs shared sensitivity to many PI3K/mTOR inhibitors. Altogether, we show distinct genomic and transcriptomic signatures in PM-ccRCC, highlight the superiority of transcriptomics in interpreting drug sensitivities, and encourage the use of TKIs and PI3K/mTOR inhibitors in PM-ccRCC.
Insights
Pancreatic metastases from clear-cell renal cell carcinoma (ccRCC) show unique genomic and transcriptomic profiles. These findings support using tyrosine kinase inhibitors and PI3K/mTOR inhibitors for treatment.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Clear-cell renal cell carcinoma (ccRCC) is a common primary cancer for pancreatic metastases (PM).
- Previous studies suggest distinct genomic features, angiogenesis, and tyrosine kinase inhibitor (TKI) sensitivity in PM-ccRCC.
- No functional or single-cell studies have explored these metastatic lesions.
Purpose of the Study:
- To investigate the genomic, single-cell transcriptomic, and drug sensitivity profiles of patient-derived cells (PDCs) from PM-ccRCC.
- To identify distinct molecular signatures and potential therapeutic targets in PM-ccRCC.
- To correlate transcriptomic data with observed drug sensitivities.
Main Methods:
- Recruitment of five patients with PM-ccRCC.
- Genomic profiling of patient-derived cells (PDCs).
- Single-cell RNA sequencing (scRNA-seq) for transcriptomic analysis.
- Drug sensitivity assays on PDCs.
Main Results:
- PM-ccRCC PDCs exhibited both known and novel genomic alterations.
- Transcriptomic profiles of PM-ccRCC PDCs differed from primary and metastatic ccRCC, with upregulated angiogenesis and PI3K/mTOR pathways.
- Integrated data analysis revealed transcriptomics as the best predictor of drug sensitivities.
- PM-ccRCC PDCs demonstrated sensitivity to multiple PI3K/mTOR inhibitors.
Conclusions:
- PM-ccRCC possesses distinct genomic and transcriptomic signatures.
- Transcriptomic analysis is superior for interpreting drug sensitivities in PM-ccRCC.
- Tyrosine kinase inhibitors (TKIs) and PI3K/mTOR inhibitors are promising therapeutic options for PM-ccRCC.
