出 处:《中国免疫学杂志》2024年第8期1671-1676,共6页Chinese Journal of Immunology
基 金:2021年厦门市医疗卫生指导性项目(3502Z20214ZD1254)。
摘 要:目的:探究CENPF在肾透明细胞癌(KIRC)中的表达及临床意义。方法:利用UALCAN和HPA数据库分析CENPF在KIRC与癌旁组织中的表达差异;通过GEPIA数据库分析CENPF基因与KIRC患者临床病理学参数及预后的关系;通过TIMER数据库分析CENPF与KIRC免疫浸润水平的关系;基于UALCAN数据库调取TCGA数据库中KIRC患者CENPF的共表达基因,并进行GO聚类分析和KEGG分析。通过转染siRNA干扰ACHN和786-O细胞中CENPF的表达并通过RT-PCR和Western blot方法进行验证。采用CCK-8、Transwell和细胞克隆形成实验探究CENPF在肾癌细胞系中下调表达后对ACHN和786-O细胞的增殖、迁移和细胞克隆形成能力的影响。结果:根据数据库显示在KIRC患者中CENPF的表达显著增加。CENPF高表达与总体存活率(OS)和无病存活率(DFS)呈负相关。KIRC患者中CENPF表达量与其肿瘤微环境中的肿瘤细胞纯度、巨噬细胞、CD8+T细胞、CD4+T细胞、中性粒细胞和树突状细胞表达丰度呈显著正相关;相关功能网络分析表明CENPF可能通过调控细胞周期、细胞有丝分裂和DNA修复等途径参与KIRC发生。此外,CENPF的mRNA表达在肾癌细胞系中也有增加。CCK-8实验表明CENPF基因沉默抑制ACHN和786-O细胞增殖。Transwell实验结果表明,CENPF基因沉默对KIRC细胞迁移能力有明显影响。细胞克隆形成实验结果表明,干扰CENPF基因表达抑制了786-O细胞的克隆形成能力。结论:本研究表明CENPF在KIRC进展中起关键作用。CENPF作为KIRC的预后指标和潜在靶点具有前瞻性的临床意义。Objective:To investigate the expression and clinical significance of CENPF in renal clear cell carcinoma(KIRC).Methods:The UALCAN and HPA databases were applied to analyze the difference in expression of CENPF in KIRC compared with paracancerous tissue the relationship between CENPF gene and clinicopathological parameters and prognosis of KIRC patients were analyzed by the GEPIA database;the relationship between CENPF and immune infiltration level of KIRC were analyzed by the TIMER database;the UALCAN database was used to analyze the co-expression network of CENPF genes in TCGA KIRC patients,GO enrichment analysis and KEGG enrichment analysis were performed on the basis of the co-expression network.CCK-8,Transwell and clone formation assays were used to investigate the effect of CENPF down-regulated expression in renal cancer cell lines on the proliferation,migration and clone formation of ACHN and 786-O cells.Results:CENPF expression was significantly highly expressed in KIRC patients.High CENPF expression was negatively correlated with overall survival(OS)and disease-free survival(DFS).The expression of CENPF in KIRC patients were significantly and positively correlated with tumor cell purity,macrophages,CD8+T cells,CD4+T cells,neutrophils and dendritic cells in tumor microenvironment.The correlation network analysis indicated that CENPF may be involved in the development of KIRC through the regulation of cell cycle,cell mitosis and DNA repair.In addition,CENPF mRNA expression was also increased in renal cancer cell lines.CCK-8 assay showed that CENPF knockdown inhibited the proliferation of ACHN and 786-O cells.Transwell assay results indicated that CENPF knockdown suppressed the migration of KIRC cells.The results of cell clonal formation experiment showed that interference with CENPF gene expression inhibited the clonal formation ability of 786-O cells.Conclusion:This study suggests that CENPF plays a key role in the progression of KIRC.CENPF has prospective clinical significance as a prognostic indicator an
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