| 摘要: |
| 目的 探讨泛素折叠修饰因子1特异性肽酶结构域蛋白（ZUP1）基因在乳腺癌中的表达情况及上下游机制。方法 使用基因表达汇编（GEO）、癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库，检索收集乳腺癌患者的基因信息和临床病理数据，通过χ2检验分析乳腺癌组织中ZUP1基因表达与临床病理因素的关系，使用Kaplan-Meier生存分析探讨乳腺癌患者生存状况与ZUP1表达的关系。用生物信息学方法预测潜在调控ZUP1的miRNA和泛素连接酶，最后进行基因集富集分析。结果 ZUP1基因在乳腺癌组织中的表达高于正常对照组织。ZUP1表达水平与乳腺癌T分期、PAM50分型、雌激素受体状态、孕激素受体状态、人表皮生长因子受体2状态和组织学类型有关（P均<0.01），ZUP1高表达组患者的总生存时间低于ZUP1低表达组（P=0.031）。生物信息学预测结果显示，以ZUP1基因为靶点的差异表达最显著的10个miRNA为miRNA-10b-3p、miRNA-499a-5p、miRNA-181b-2-3p、miRNA-181b-3p、miRNA-4420、miRNA-548aw、miRNA-5680、miRNA-570-3p、miRNA-7156-5p和miRNA-8087，包括MARCH1、MARCH8、Mdm2、synoviolin和MIB1在内的E3泛素连接酶可能调节ZUP1蛋白表达。基因集富集分析结果表明ZUP1在乳腺癌中主要参与基础转录因子、泛素介导的蛋白质水解、卵母细胞减数分裂、RNA降解和极光激酶B等通路。结论 ZUP1在乳腺癌中表达上调，与患者预后具有相关性。ZUP1在乳腺癌发生、发展中的上下游机制与多种miRNA和多条信号通路有关。 |
| 关键词: 泛素折叠修饰因子1特异性肽酶结构域蛋白 乳腺肿瘤 存活率分析 生物标志物 生物信息学 |
| DOI：10.16781/j.0258-879x.2020.12.1338 |
| 投稿时间：2020-08-30修订日期：2020-12-09 |
| 基金项目: |
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| Expression and mechanisms of ZUP1 in breast cancer: a bioinformatics analysis |
| ZHANG Guang-jun,TU Gang* |
(Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the expression and upstream/downstream mechanisms of ubiquitin fold modifier 1-specific peptidase domain protein (ZUP1) in breast cancer. Methods Gene information and clinicopathological data of breast cancer patients were retrieved using Gene Expression Omnibus (GEO), Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The relationships between the expression of ZUP1 and clinicopathological factors/survival status of breast cancer patients were analyzed by χ2 test and Kaplan-Meier survival analysis, respectively. Bioinformatics methods were used for prediction of miRNAs and ubiquitin ligase that could potentially regulate ZUP1. Finally, the gene set enrichment analysis (GSEA) was performed. Results The expression of ZUP1 was higher in breast cancer tissues than in normal control tissues, and was related to T stage, PAM50 classification, statuses of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and histological type of breast cancer (all P<0.01). The overall survival time of patients with high expression of ZUP1 was significantly lower than that of patients with low expression of ZUP1 (P=0.031). Bioinformatics predicted that the top 10 miRNAs targeting ZUP1 with the highest differential expression were miRNA-10b-3p, miRNA-499a-5p, miRNA-181b-2-3p, miRNA-181b-3p, miRNA-4420, miRNA-548aw, miRNA-5680, miRNA-570-3p, miRNA-7156-5p and miRNA-8087. E3 ubiquitin ligase including MARCH1, MARCH8, Mdm2, synoviolin and MIB1 may regulate the expression of ZUP1. The GSEA results indicated that ZUP1 was mainly involved in basic transcription factor, ubiquitin mediated proteolysis, oocyte meiosis, RNA degradation and Aurora B pathway. Conclusion The expression of ZUP1 is up-regulated in breast cancer, and is related to prognosis. The upstream and downstream mechanisms of ZUP1 in the development and progression of breast cancer are related to a variety of miRNAs and multiple signaling pathways. |
| Key words: ubiquitin fold modifier 1-specific peptidase domain protein breast neoplasms survival analysis biomarkers bioinformatics |
