Centromere Protein F (CENPF) Serves as a Potential Prognostic Biomarker and Target for Human Hepatocellular Carcinoma

Abstract

Overexpression of Centromere Protein F ( CENPF ) is associated with tumorigenesis of many human malignant tumors. But the molecular mechanism and prognostic value of CENPF in patients with hepatocellular carcinoma (HCC) are still unclear. In this essay, expression of CENPF in HCC tumors were evaluated in a series of databases, including GEO, TCGA, Oncomine, GEPIA, The Human Protein Atlas and Kaplan-Meier plotter. It was apparent that mRNA and protein expression levels of CENPF were significantly increased in patients with HCC and were manifestly associated with the tumor stage of HCC. Aberrant expressions of CENPF were significantly linked with worse overall survival (OS) and progression-free survival (PFS) in HCC patients. Then, immunohistochemistry of CENPF in human HCC samples was carried out to suggest that CENPF protein was over-expressed in HCC tissues, compared with paired adjacent non-cancerous samples. And small interfering RNAs of CENPF in the human HepG2 cells were further performed to reveal that down-regulation of CENPF significantly inhibited cell proliferation, cell migration, and cell invasion, but slightly promoted cell apoptosis in human HepG2 cells. Moreover, the gene-set enrichment analysis (GSEA) was conducted to probe the biology process and molecular signaling pathway of CENPF in HCC. The GSEA analysis pointed out that CENPF was principally enriched in cell cycle and closely related to E2F1 and CDK1 in the regulation of cell cycle, especially during G2/M transition of mitosis in HCC. Additionally, immune infiltration analysis by CIBERSORTx revealed that mutilpe immune cells, including T reg , etc., were significantly different in HCC samples with CENPF high , compared with CENPF low . These results collectively demonstrated that CENPF might serve as a potential prognostic biomarker and novel therapeutic target for HCC. However, further research is needed to validate our findings and promote the clinical application of CENPF in HCC.

CENPF/CDK1 signaling pathway enhances the progression of adrenocortical carcinoma by regulating the G2/M-phase cell cycle

“…Huang Y et al . asserted that up-regulation of CENPF was a hazard factor for the prognosis of HCC [ 21 ]. A recent study suggested that overexpressed CENPF exerted as a cancer-driver gene in the formation and development of human cancers [ 48 ].…”

“…The expression peak of CENPF is in the cell cycle of the G2/M phase. The aberrant expression of CENPF has been found in multiple malignancies, including hepatocellular carcinoma (HCC) [ 19 – 21 ], prostate cancer [ 22 ], and other carcinomas [ 23 , 24 ], but little literature about ACC. Specifically, the latest studies have acclaimed that overexpression of CENPF markedly promoted cell proliferation in HCC [ 20 ] and induced tumor metastasis in prostate cancer with a poor prognosis [ 25 ].…”

Single-cell transcriptomics analysis reveals intratumoral heterogeneity and identifies a gene signature associated with prognosis of hepatocellular carcinoma

“…TOP2A has been reported to be up-regulated in HCC and could be used as a biological indicator to predict HCC prognosis [ 24 ]. CENPF associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in HCC [ 25 ]. In addition, GSVA results showed that proliferation biological pathways, such as mitosis, G 2 /M checkpoint, and E2F targets, were enriched in hepatocytes C4.…”

LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme

“…High expression of FLVCR1 was significantly associated with poor prognostic value in HCC patients [ 34 ]. CENPF was identified as a potential prognostic biomarker and target for HCC [ 35 ]. It is reported that upregulated RECQL4 [ 36 ], SPC24 [ 37 ], and KIF20A [ 38 ] could predict poor prognosis in HCC, whereas upregulated ZWINT was associated with great prognosis in patients with HCC after surgery [ 39 ].…”