基于Oncomine和TCGA数据库分析E2F5在前列腺癌组织中的表达及临床意义

目的:通过数据挖掘分析E2F5在前列腺癌（PCa）组织中的表达及临床意义。 方法:基于GEPIA、Oncomine数据库分析E2F5在PCa中的差异性表达及其与预后的关系。高通量基因芯片筛选敲低E2F5差异表达的基因并应用Western blot验证。结果:E2F5 mRNA在PCa组织中表达明显高于正常前列腺组织（P＜0.001）。LinkedOmics数据库分析显示E2F5 mRNA在不同T分期（P＜0.001）和N分期（P＜0.05）中存在差异性表达。在Oncomine数据库中Taylor Prostate 3芯片数据中，Gleason评分≤3+4患者PCa组织中E2F5 mRNA表达水平显著低于Gleason≥ 4+3的患者（P＜0.05）；T2期患者PCa组织中E2F5 mRNA表达水平显著低于T3+T4期的患者（P＜0.05）；未复发患者PCa组织中E2F5 mRNA表达水平显著低于复发的患者（P＜0.01）。基因芯片结果显示:敲低E2F5表达水平后，310个基因显著上调，228个基因显著下调。KEGG富集分析结果表明，下调E2F5后主要影响p53、细胞周期、Wnt等信号通路。Western blot证实下调E2F5后CDK6和CDC25A蛋白表达水平下降。结论:在PCa中E2F5的表达与患者的Gleason评分、T分期、N分期及复发与否有一定的相关性。E2F5通过调控周期相关的基因促进PCa的进展。

Analysis of the expression and clinical significance of E2F5 in prostate cancer based on Oncomine and TCGA database

Objective:To analyze the expression and clinical significance of E2F5 in prostate cancer based on TCGA database.Methods:The differential expression of E2F5 and the association between E2F5 and clinical prognosis in prostate cancer was analyzed based on the GEPIA and Oncomine databases.RNA-seq analysis was performed to analyze the gene expression profile affected by E2F5 knockdown.Results:The analysis based on the GEPIA showed that the mRNA expression of E2F5 in prostate cancer tissue was significantly higher than that in normal tissue(P＜0.001).The LinkedOmics database showed a positive correlation between the mRNA expression of E2F5 and T stage(P＜0.001)and N stage(P＜0.05).Data acquired from Taylor Prostate 3 cohort via Oncomine database showed that the level of E2F5 was inversely associated with Gleason score(P＜0.05),N stage(P＜0.05)and recurrence status(P＜0.01).Hierarchical clustering revealed a total of 310 upregulated genes and 228 downregulated genes in PC-3 cells transfected with E2F5 siRNA.The KEEG Enrichment analysis showed that E2F5 knockdown primarily affected the signaling pathway gene sets,including the p53 signaling pathway,cell cycle and Wnt signaling pathway.The expression of CDK6 and CDC25A protein decreased in cells transfected with si-E2F5.Conclusion:The expression level of E2F5 mRNA is significantly correlated with with Gleason score,T stage,N stage and recurrence status in patients with prostate cancer.E2F5 may promote the progression of prostate cancer by regulating cell cycle related genes.