锌指蛋白521在肾母细胞瘤的表达及转录调控预测研究

doi:10.3969/j.issn.1009-976X.2020.06.019

摘要/Abstract

摘要： 目的探究锌指蛋白521（ZNF521）在肾母细胞瘤中的表达和诊断价值,预测ZNF521相关基因及靶基因,分析相关功能及调控机制。方法基于TARGET、GTEx和GEO数据库中RNA-seq数据,筛选肾母细胞瘤差异基因,计算ZNF521在肾母细胞瘤中的表达并使用诊断Meta分析评估诊断效能。使用Pearson相关分析筛选出ZNF521的相关基因,进行富集分析。基于Cistrome DB下载ZNF521的ChIP-Seq数据预测ZNF521潜在靶基因,将肾母细胞瘤差异基因、ZNF521相关基因以及潜在靶基因取交集作为最佳潜在靶基因,构建蛋白互作网络进行功能注释。结果共纳入185例肾母细胞瘤组织和69例非肿瘤肾组织的RNA-seq数据,ZNF521在肿瘤组织中高表达（SMD=3.385,95%CI： 1.024~5.747,P=0.005）,SROC曲线下面积为0.990（95%CI：0.970~0.990）。富集分析显示,ZNF521相关基因显著富集的功能和疾病包括DNA复制、细胞周期、肾脏发育、泌尿系统癌症。最终获得101个最佳潜在靶基因,其中FGFR1涉及细胞代谢、细胞分裂、胚胎发育等多个生物过程,并且在蛋白互作网络中与存在相似功能的IGF2、EZH2存在潜在互作关系。结论 ZNF521在肾母细胞瘤样本中高表达,ZNF521相关基因及最佳预测靶基因与肾母细胞瘤密切相关,可能作为临床上肾母细胞瘤诊断治疗的潜在靶点。

关键词: 肾母细胞瘤, 转录因子, 锌指蛋白521, 诊断性meta分析, 生物信息学

Abstract: Objective To investigate the expression and diagnostic value of zinc finger protein 521 （ZNF521） in nephroblastoma. The related genes and target genes of ZNF521 are predicted, and the related functions and regulatory mechanisms are analyzed. Methods Based on the RNA-seq data in the TARGET, GTEx, and GEO databases, the differential genes of nephroblastoma were screened, the expression of ZNF521 in nephroblastoma was calculated and the diagnostic Meta-analysis was used to evaluate the diagnostic efficacy. Pearson correlation analysis was used to screen out the related genes of ZNF521 and perform enrichment analysis. Based on the ChIP-Seq data of ZNF521 downloaded from the Cistrome DB website, the potential target genes of ZNF521 are predicted, and the intersection of nephroblastoma differential genes, ZNF521-related genes, and potential target genes is taken as the best potential target genes, function annotation analysis is performed by constructing protein-protein interaction （PPI） network. Results A total of 185 cases of nephroblastoma tissues and 69 cases of non-tumor kidney tissues were included in RNA-seq data. ZNF521 was highly expressed in tumor tissues （SMD=3.385, 95%CI： 1.024~5.747,P=0.005）, the under area of SROC curve is 0.990 （95%CI： 0.970~0.990）. Enrichment analysis showed that the significantly enriched functions and diseases of ZNF521 related genes include DNA replication, cell cycle, kidney development, and urinary system cancer. Finally, the 101 best potential target genes were obtained. Among them, FGFR1 is involved in multiple biological processes such as cell metabolism, cell division, embryonic development, and has a potential interaction relationship with IGF2 and EZH2 that have similar functions in PPI. Conclusion ZNF521 is highly expressed in nephroblastoma samples. ZNF521-related genes and the best-predicted target genes are closely related to nephroblastoma and may serve as potential targets for clinical diagnosis and treatment of nephroblastoma.

Key words: diagnostic meta-analysis, nephroblastoma, zinc finger protein 521, transcription factor, bioinformatics

中图分类号:

R737.11

胡师华, 韦康来. 锌指蛋白521在肾母细胞瘤的表达及转录调控预测研究[J]. 岭南现代临床外科, 2020, 20(06): 774-783.

HU Shi-hua, WEI Kang-lai. Expression and transcriptional regulatory function prediction of zinc finger protein 521 in nephroblastoma[J]. Lingnan Modern Clinics in Surgery, 2020, 20(06): 774-783.

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