Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Sep 21, 2026

Cyclin F (CCNF) is implicated in multiple cancers, while its prognostic value in clear cell renal cell carcinoma (ccRCC) is not established. This study evaluates cyclin F using immunohistochemical staining across two independent ccRCC tissue array cohorts (TMA_1 and TMA_2), plus bioinformatics analysis of TCGA and GEO mRNA datasets. Cyclin F/CCNF is elevated in tumors versus NAT and normal tissues, associates with aggressive features, and predicts shorter overall survival. Multivariable analysis identifies CCNF-high expression as an independent marker of poor prognosis. Mechanistic enrichment suggests CCNF-driven signaling for uncontrolled proliferation, alongside links to tumor immune infiltration, shaping clinical outcomes and highlighting a biomarker and therapeutic target potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Background

Cyclin F/CCNF in cancer

Clinical challenges in ccRCC

Methods

Immunohistochemistry on tissue arrays

Bioinformatics using TCGA and GEO

Immune infiltration analyses

Results

CCNF expression in tumor versus normal tissues

Association with aggressive clinicopathological features

Survival association and independent prognosis

Mechanistic insights

Enriched signaling pathways and immune microenvironment

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma Maciej Kwiatkowski2, Adrian Krajewski3, Justyna Durślewicz1, Karolina Buchholz1,3, Dariusz Grzanka1, Maciej Gagat3,5, Jan Zabrzyński4 & Anna Klimaszewska‑Wiśniewska1* Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_ 1 and tissue microarray (TMA)_ 2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non‑cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF‑high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF‑high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor‑infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC. Renal cell carcinoma (RCC) accounts for approximately 2% of cancer-related diagnoses and deaths globally. Its incidence rate has increased in the last decades, attributed to incidental diagnoses associated with the extensive use of imaging techniques1,2. Clear-cell RCC (ccRCC) represents the predominant and simultaneously the most lethal histological subtype of RCC tumors3. When diagnosed early, ccRCC can be successfully managed with surgery. Nevertheless, due to its typically asymptomatic nature, nearly 28% of cases are initially diagnosed with regional or distant metastases4. 1Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland. 2Department of Urology and Urological Oncology, Multidisciplinary Hospital of Ludwik Blażek, Inowrocław, Poland. 3Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland. 4Department of Orthopaedics and Traumatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University inToruń, Bydgoszc

FAQs

What was the main goal of the study on cyclin F/CCNF in ccRCC?

To determine whether cyclin F/CCNF expression can serve as a prognostic marker in clear cell renal cell carcinoma and relate it to clinicopathological features and patient outcomes.

How was cyclin F expression measured in tumor tissues?

Cyclin F was assessed by immunohistochemical staining using two independent ccRCC tissue array cohorts (TMA_1 and TMA_2) and compared with adjacent normal tissues and normal kidney samples.

Does high CCNF expression affect patient survival in ccRCC?

Yes. Across analyzed cohorts, tumors with cyclin F/CCNF-high expression showed shorter overall survival, and multivariable analysis identified CCNF-high expression as an independent prognostic factor for poor overall survival.

Sep 21, 2026

Uploaded by Emma Wilson