4.6 Article

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

期刊

JOURNAL OF CANCER
卷 12, 期 10, 页码 2933-2951

出版社

IVYSPRING INT PUBL
DOI: 10.7150/jca.52187

关键词

CENPF; HCC; hepatocellular carcinoma; biomarker; survival; prognostic value; bioinformatics analysis

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资金

  1. National Natural Science Foundation of China [81600436, 81970488]

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Overexpression of Centromere Protein F (CENPF) is significantly correlated with tumorigenesis and poor prognosis in hepatocellular carcinoma (HCC) patients. Down-regulation of CENPF inhibits cell proliferation, migration, and invasion, while slightly promoting apoptosis in human HepG2 cells. Gene-set enrichment analysis (GSEA) reveals that CENPF is mainly enriched in cell cycle regulation, particularly during G2/M transition of mitosis in HCC. Immune infiltration analysis shows significant differences in immune cell populations in HCC samples with different levels of CENPF expression. These findings suggest that CENPF may serve as a potential prognostic biomarker and therapeutic target for HCC.
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 CENPFhigh, compared with CENPFlow. 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.

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