Huang Yugang, Chen Xiuwen, Wang Li, Wang Tieyan, Tang Xianbin, Su Xiaomin
Department of Pathology, Taihe Hospital, Hubei University of Medicine, Hubei 44200, China.
Department of Immunology, Nankai University School of Medicine, Tianjin 300110, China.
J Cancer. 2021 Mar 15;12(10):2933-2951. doi: 10.7150/jca.52187. eCollection 2021.
Overexpression of Centromere Protein F () is associated with tumorigenesis of many human malignant tumors. But the molecular mechanism and prognostic value of in patients with hepatocellular carcinoma (HCC) are still unclear. In this essay, expression of 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 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 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 in the human HepG2 cells were further performed to reveal that down-regulation of 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 in HCC. The GSEA analysis pointed out that was principally enriched in cell cycle and closely related to and 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, etc., were significantly different in HCC samples with CENPF, compared with CENPF. These results collectively demonstrated that 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 in HCC.
着丝粒蛋白F（CENPF）的过表达与多种人类恶性肿瘤的发生相关。但CENPF在肝细胞癌（HCC）患者中的分子机制及预后价值仍不清楚。在本文中，我们在一系列数据库中评估了CENPF在HCC肿瘤中的表达，这些数据库包括GEO、TCGA、Oncomine、GEPIA、人类蛋白质图谱和Kaplan-Meier绘图仪。很明显，HCC患者中CENPF的mRNA和蛋白表达水平显著升高，且与HCC的肿瘤分期明显相关。CENPF的异常表达与HCC患者较差的总生存期（OS）和无进展生存期（PFS）显著相关。然后，对人类HCC样本进行CENPF免疫组化，结果表明与配对的相邻非癌样本相比，CENPF蛋白在HCC组织中过表达。进一步在人类HepG2细胞中进行CENPF的小干扰RNA实验，结果显示CENPF的下调显著抑制了人类HepG2细胞的增殖、迁移和侵袭，但略微促进了细胞凋亡。此外，进行基因集富集分析（GSEA）以探究CENPF在HCC中的生物学过程和分子信号通路。GSEA分析指出，CENPF主要富集于细胞周期，且在细胞周期调控中与CCNB1和CDC20密切相关，尤其是在HCC有丝分裂的G2/M期转换过程中。另外，通过CIBERSORTx进行的免疫浸润分析显示，与无CENPF的HCC样本相比，有CENPF的HCC样本中包括T细胞等多种免疫细胞存在显著差异。这些结果共同表明，CENPF可能作为HCC潜在的预后生物标志物和新型治疗靶点。然而，需要进一步研究来验证我们的发现，并推动CENPF在HCC中的临床应用。
