Abstract
Centromere protein F (CENPF), a protein related to the cell cycle, is a key part of the kinetochore-centromere complex involved in cell division, differentiation, and proliferation. CENPF expression is upregulated in various types of cancer and plays a role in oncogenesis and tumor progression. However, the expression pattern, prognostic significance, and biological role of CENPF in these cancer types are poorly understood. Therefore, in this study, we conducted a pan-cancer analysis of the role of CENPF, which we considered a cut point, to investigate its utility as a prognostic and immunological indicator for malignancies, especially cholangiocarcinoma (CCA). Using systematic bioinformatics analysis, we investigated the expression patterns, prognostic relevance, molecular function, signaling pathways, and immune infiltration patterns of CENPF in the pan-cancer analysis. Western blot and immunohistochemistry staining assays were performed to evaluate the expression profiles of CENPF in CCA tissues and cell lines. Furthermore, Cell Counting Kit-8, colony formation, wound healing, and Transwell assays, as well as CCA xenograft mouse models, were employed to determine the role and function of CENPF in CCA. The results showed that CENPF expression was upregulated and strongly linked to a worse prognosis in most cancer types. CENPF expression was substantially associated with immune cell infiltration, tumor microenvironment, genes related to immune checkpoints, tumor mutational burden, microsatellite instability, and immunotherapy response in diverse malignancies. CENPF was considerably overexpressed in CCA tissues and cells. Functionally, inhibiting CENPF expression significantly reduced the proliferating, migrating, and invading abilities of CCA cells. CENPF expression also affects the prognosis of multiple malignancies, which is highly associated with immunotherapy response and tumor immune cell infiltration. In conclusion, CENPF may act as an oncogene and an immune infiltration-related biomarker and can accelerate tumor development in CCA.
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Data and materials generated are relevant to the results that are included in this article. Other data are available from the corresponding author upon reasonable request.
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The authors thank a professional English editor (Bullet Edits) for assistance in improving the quality of the language.
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This study was funded by the Clinical Medical Technology Innovation Guidance Project of Hunan province (2021SK53522).
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Z.C., L.Z., and J.Z. conceived and designed the study. J.Z. provided the funding for the study. Z.C. and L.Z. performed the experiment and collected the data. Z.W. and X.W. analyzed the data. Z.C. and L.Z. wrote the manuscript. Z.W. and X.W. reviewed or edited the manuscript. All authors have read and approved the final manuscript version.
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Approval to obtain experimental tissues from patients with cholangiocarcinoma and normal controls was obtained under informed consent. This study was reviewed, performed, and approved in accordance with the ethical standards as laid down in the Declaration of Helsinki by the Ethic Committee of the Second Xiangya Hospital of the Central South University ((2022) Clinical Study Review No. 095).
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Cao, Z., Zeng, L., Wang, Z. et al. Integrated pan-cancer analysis of centromere protein F and experimental verification of its role and clinical significance in cholangiocarcinoma. Funct Integr Genomics 23, 190 (2023). https://doi.org/10.1007/s10142-023-01108-x
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DOI: https://doi.org/10.1007/s10142-023-01108-x