Related Experiment Video
Updated: Jan 9, 2026
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.
More Related Videos
09:32Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
05:36Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Related Concept Videos
02:23Abnormal Proliferation
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...