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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
RPA1, RFC1, and POLE Expression in Clear Cell Renal Cell Carcinoma: Immune and Clinical Relevance
Michał Gola1,2, Jacek Kieżun3, Bartłomiej Emil Kraziński3
1Department of Anatomy and Histology, School of Medicine, University of Warmia and Mazury, Olsztyn, Poland; michal.gola@uwm.edu.pl.
Background/Aim:
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer with aggressive behavior and poor prognosis. Dysregulation of DNA replication and repair, including alterations in replication protein A1 (RPA1), replication factor C subunit 1 (RFC1), and DNA polymerase epsilon (POLE), may influence tumor biology and immune interactions. This study investigated the expression of these proteins in ccRCC and their associations with systemic inflammation, tumor immune microenvironment (TME), and prognosis.
Materials And Methods:
Immunohistochemical expression of RPA1, RFC1, and POLE was evaluated in 52 ccRCC and adjacent normal tissues, with correlations to clinical data and preoperative blood parameters. Transcriptomic data from The Cancer Genome Atlas (TCGA) and immune deconvolution analyses (TIMER2.0, ConsensusTME) validated findings and explored associations with immune infiltration and survival.
Results:
Tumor tissues showed increased RPA1 and decreased RFC1 expression, while POLE was unchanged. Elevated RPA1 correlated with reduced systemic inflammation, while low RFC1 correlated with larger tumor size. High POLE levels associated with lower preoperative platelet-to-lymphocyte ratio and an inverse trend with T stage. TCGA data confirmed these findings, showing that low RPA1 and RFC1 predicted poorer outcomes, while reduced POLE and RFC4 were linked to improved survival. TIMER2.0 analysis revealed that high RPA1 and RFC1 expression was linked to increased macrophage and neutrophil infiltration, whereas high POLE to CD4+ T-cell infiltration. Notably, RPA1, RFC1, and POLE expression correlated with immune-checkpoint molecules (including PD-L1, VISTA, and CTLA-4), suggesting implications for immunotherapy responsiveness. Immune TME composition, as estimated by ConsensusTME, influenced survival outcomes, with replication protein expression modulating prognostic relevance of immune subpopulations.
Conclusion:
DNA replication proteins interact with systemic inflammation and the TME in ccRCC, supporting their role as biomarkers and potential therapeutic targets.
Insights
DNA replication proteins RPA1, RFC1, and POLE impact clear cell renal cell carcinoma (ccRCC) progression and immune interactions. Their expression levels correlate with inflammation, tumor microenvironment, and patient survival, suggesting potential as biomarkers and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer with poor prognosis.
- Dysregulation of DNA replication and repair proteins, including RPA1, RFC1, and POLE, may affect ccRCC biology and immune responses.
Purpose of the Study:
- To investigate the expression of RPA1, RFC1, and POLE in ccRCC.
- To analyze associations between these proteins, systemic inflammation, the tumor immune microenvironment (TME), and patient prognosis.
Main Methods:
- Immunohistochemistry was used to assess RPA1, RFC1, and POLE expression in ccRCC tissues.
- Correlations were examined with clinical data, blood parameters, and TCGA transcriptomic data.
- Immune deconvolution analyses (TIMER2.0, ConsensusTME) explored associations with immune infiltration and survival.
Main Results:
- Tumor tissues showed increased RPA1 and decreased RFC1 expression; POLE was unchanged.
- RPA1, RFC1, and POLE expression correlated with systemic inflammation markers, tumor characteristics, and immune cell infiltration (macrophages, neutrophils, CD4+ T-cells).
- Expression of these proteins was linked to immune-checkpoint molecules and influenced survival outcomes, modulating the prognostic relevance of immune subpopulations.
Conclusions:
- DNA replication proteins RPA1, RFC1, and POLE are significantly associated with systemic inflammation and the TME in ccRCC.
- These proteins show potential as prognostic biomarkers for ccRCC.
- RPA1, RFC1, and POLE represent potential therapeutic targets for ccRCC treatment.
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