A Comprehensive Analysis of the Prognostic, Immunological and Diagnostic Role of CCNF in Pan-cancer

Xiaofeng Gao; Huitong Bu; Juanjuan Ge; Xuzheng Gao; Ying Wang; Zhenwang Zhang; Long Wang

doi:10.7150/jca.86597

A Comprehensive Analysis of the Prognostic, Immunological and Diagnostic Role of CCNF in Pan-cancer

J Cancer. 2023 Jul 31;14(13):2431-2442. doi: 10.7150/jca.86597. eCollection 2023.

Authors

Xiaofeng Gao^{1

2}, Huitong Bu³, Juanjuan Ge², Xuzheng Gao¹, Ying Wang¹, Zhenwang Zhang^{1

2}, Long Wang^{1

2

4}

Affiliations

¹ School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437000, Hubei, PR China.
² Medicine Research Institute /Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437000, Hubei, PR China.
³ College of Biology, Hunan University, Hunan, Changsha, 410012, PR China.
⁴ School of Stomatology and Ophthalmology, Xianning Medical College, Hubei University of Science and Technology, Xianning 437000, Hubei, PR China.

Abstract

Background: Cyclin F (CCNF) represents a pivotal constituent within the family of cell cycle proteins, which also belongs to the F-box protein family and acts as a critical regulatory factor in cell cycle transition. Its heightened expression has been consistently identified across various cancer types, including breast, pancreatic, and colorectal cancer. Nonetheless, a comprehensive exploration of CCNF's involvement in pan-cancer remains lacking. Methods: This study collected transcriptomic data and clinical information from several databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and BioGPS detabase. Employing bioinformatics methods, we investigated the potential oncogenic role of CCNF, utilizing various databases such as cBioPortal, Human Protein Atlas (HPA), TIMER2, UALCAN, GEPIA, GSCALite, and CTD detabase. These analyses focused on exploring CCNF expression, prognosis, gene mutations, immune cell infiltration, DNA methylation levels, and targeted chemical drugs across different tumor types. Additionally, we obtained CCNF-related genes from GeneMANIA and GEPIA databases and conducted GO and KEGG enrichment analyses to gain deeper insights into the biological processes associated with CCNF. Furthermore, we validated the differential expression of CCNF in normal human breast cancer and breast cancer cell lines using experimental verification. Results: CCNF exhibited upregulation in the majority of cancer types, demonstrating early diagnostic potential in 15 cancers and prognostic implications for adverse outcomes across numerous malignancies. Furthermore, CCNF was found to be linked with markers of the tumor immune microenvironment in various cancers. Additionally, CCNF expression influenced genetic alterations in pan-cancer. Enrichment analysis revealed that CCNF primarily participates in crucial biological pathways such as the cell cycle, p53 signaling pathway, and cellular senescence pathways. RT-qpcr and WB assays further confirmed that CCNF expression was higher in human cancer cell lines than in normal cell lines. Conclusion: The underlying role and mechanism of CCNF in pan-cancer were elucidated through comprehensive bioinformatics analysis and experimental validation. CCNF holds promise as an invaluable early detection indicator and tumor biomarker, offering potential targets for tumor treatment and prevention.

Keywords: Biomarkers; CCNF; Diagnosis; Immunization; Pan-Cancer; Prognosis.