Increased expression of Cyclin F in liver cancer predicts poor prognosis

Yang, Zelong; Han, Yang; Guo, Tao; Wang, Yifei; He, Kai; Hu, Haoran; Chen, Yong

doi:10.1097/md.0000000000026623

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…These two reports suggest that CCNF is likely to be a tumor suppressor gene. However, studies have also shown that the overexpression of CCNF predicts a poor prognosis in ovarian cancer ( 14 ), liver cancer ( 15 ) and skin melanoma ( 16 ), suggesting that CCNF is an oncogene. Although contradictory, the above reports revealed that the functions of CCNF are likely to be related to the state of cells ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

CCNF is a potential pancancer biomarker and immunotherapy target

Wei

Xiao

et al. 2023

Front. Oncol.

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BackgroundCCNF catalyzes the transfer of ubiquitin molecules from E2 ubiquitin-conjugating enzymes to target proteins, thereby regulating the G1/S or G2/M transition of tumor cells. Thus far, CCNF expression and its potential as a pancancer biomarker and immunotherapy target have not been reported.MethodsTCGA datasets and the R language were used to analyze the pancancer gene expression, protein expression, and methylation levels of CCNF; the relationship of CCNF expression with overall survival (OS), recurrence-free survival (RFS), immune matrix scores, sex and race; and the mechanisms for posttranscriptional regulation of CCNF.ResultsCCNF expression analysis showed that CCNF mRNA expression was higher in cancer tissues than in normal tissues in the BRCA, CHOL, COAD, ESCA, HNSC, LUAD, LUSC, READ, STAD, and UCEC; CCNF protein expression was also high in many cancer tissues, indicating that it could be an important predictive factor for OS and RFS. CCNF overexpression may be caused by CCNF hypomethylation. CCNF expression was also found to be significantly different between patients grouped based on sex and race. Overexpression of CCNF reduces immune and stromal cell infiltration in many cancers. Posttranscriptional regulation analysis showed that miR-98-5p negatively regulates the expression of the CCNF gene.ConclusionCCNF is overexpressed across cancers and is an adverse prognostic factor in terms of OS and RFS in many cancers; this phenomenon may be related to hypomethylation of the CCNF gene, which could lead to cancer progression and worsen prognosis. In addition, CCNF expression patterns were significantly different among patients grouped by sex and race. Its overexpression reduces immune and stromal cell infiltration. miR-98-5p negatively regulates CCNF gene expression. Hence, CCNF is a potential pancancer biomarker and immunotherapy target.

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Section: Introductionmentioning

confidence: 99%

CCNF is a potential pancancer biomarker and immunotherapy target

Wei

Xiao

et al. 2023

Front. Oncol.

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“…Previous studies have shown that altered CCNF expression is associated with a poor prognosis in various cancers, including breast, liver, pancreatic, brain, and skin cancers 12 – 14 , 37 . In the current study, the analysis of the data from the TCGA database reveals that 45.89% of ccRCC patients are characterized by high CCNF mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…Another example is liver cancer, where an elevated level of CCNF was associated with worse OS. Additionally, this overexpression cannot be led by the mutations in the CCNF gene because only 0.81% of 372 liver cancer patients bear the mutation in CCNF locus 14 .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the IHC study by Fu et al on in-house liver cancer series showed the opposite, including the association of cyclin F-low with more aggressive tumor features and a prognosis 11 . The liver cancer studies mentioned above 11 , 14 present the opposite prognostic value of cyclin F depending on the source of data or, more precisely, the measurement level (protein vs. mRNA), leading to further controversy regarding the functional portrait of this cyclin in human cancers. We witnessed similar discrepancies in our studies on melanoma and pancreatic adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…The protein level of cyclin F increases in the S phase and peaks in the G2 phase of the cell cycle, which is strictly regulated to ensure the scheduled degradation of substrates 9 . The altered expression of cyclin F has been shown to be associated with poor prognosis of patients with various types of cancers 10 – 14 as well as the growth, metastasis, and drug resistance in some of them. Considering these findings, cyclin F emerges as a potential prognostic marker and therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

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

Kwiatkowski,

Krajewski,

Durślewicz

et al. 2024

Sci Rep

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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.

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Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

Wang

et al. 2023

CURR MED SCI

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Increased expression of Cyclin F in liver cancer predicts poor prognosis

Cited by 5 publications

References 27 publications

CCNF is a potential pancancer biomarker and immunotherapy target

CCNF is a potential pancancer biomarker and immunotherapy target

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

Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

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