RPA1, RFC1, and POLE Expression in Clear Cell Renal Cell Carcinoma: Immune and Clinical Relevance
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Anticancer Research
Institution: University of Warmia and Mazury in Olsztyn
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4416821733