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Upregulated cyclins may be novel genes for triple-negative breast cancer based on bioinformatic analysis

机译:基于生物信息分析,上调的细胞周期蛋白可以是三阴性乳腺癌的新基因

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Background Triple-negative breast cancer (TNBC) is one of the leading causes of death among females around the world. However, the molecular mechanism of the disease among TNBC patients remains to be further studied. Methods In our study, four microarray data and two high throughput sequencing data were acquired from the GEO database, and the differentially expressed genes (DEGs) between TNBC and normal tissues had been analyzed. Analysis of functional enrichment and pathway enrichment of DEGs was conducted by the Funrich software, and protein–protein interaction (PPI) network gained from the STRING, and hub genes were confirmed by the Cytoscape. Kaplan–Meier plotter (KM plotter) online dataset had been used to analyze DEGs of overall survival (OS), and progression-free survival (PFS). Results In total, 1638 DEGs were gained in our study covering 984 upregulated and 654 downregulated genes. Moreover, a PPI network was constructed, and cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), and cyclin A2 (CCNA2) were found as top genes with higher node degrees. CDK1, CCNA2, and CCNB1were obviously enriched in the cell cycle. The top upregulated genes including CDK1, CCNB1, CCNA2, and PLK1 were overexpressed in TNBC, and correlated with worse OS in breast cancer. High expression of CCNB1 was correlated with worse PFS in TNBC (HR?=?1.42, 95% CI: 1.04–1.94, P ?=? 0.028 ). Besides, there was a correlation between CCNB1 and CDK1 in TNBC, as well as between CCNA2 and CDK1 ( r ?=? 0.804 , P ?
机译:背景,三重阴性乳腺癌(TNBC)是世界各地女性中死亡的主要原因之一。然而,TNBC患者中疾病的分子机制仍有待进一步研究。在我们的研究中,从Geo数据库中获取了四种微阵列数据和两个高通量测序数据,并分析了TNBC和正常组织之间的差异表达基因(DEGS)。通过Funrich软件进行官能富集和途径富集的分析,并通过弦蛋白 - 蛋白质 - 蛋白质相互作用(PPI)网络,Cytoscape证实了轮毂基因。 Kaplan-Meier绘图仪(KM绘图仪)在线数据集已被用于分析整体生存(OS)和无进展生存(PFS)的参数。结果总计,在我们的研究中获得了1638次,涵盖了984个上调和654个下调基因。此外,构建了PPI网络,并将细胞周期蛋白依赖性激酶1(CDK1),细胞周期蛋白B1(CCNB1)和细胞周期蛋白A2(CCNA2)作为具有较高节点度的顶部基因。 CDK1,CCNA2和CCNB1在细胞周期中明显富集。包括CDK1,CCNB1,CCNA2和PLK1在内的顶部上调基因在TNBC中过表达,并与乳腺癌中的更糟的OS相关。 CCNB1的高表达与TNBC中的更差(HR?=β1.42,95%CI:1.04-1.94,P?= 0.028)相关。此外,TNBC中CCNB1和CDK1之间存在相关性,以及CCNA2和CDK1(R?= 0.804,p≤0.001;r≤x≤0.0.577,p≤0.001)。结论我们的研究结果表明,Cyclin CDK1,CCNB1和CCNA2在TNBC过表达,它们可以作为新型生物标志物,用于TNBC的诊断和治疗。

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