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基于生物信息学鉴定促进脐血源性内皮祖细胞独特生物学特征的潜在枢纽基因和信号通路。

Identification of Potential Hub Genes and Signal Pathways Promoting the Distinct Biological Features of Cord Blood-Derived Endothelial Progenitor Cells Via Bioinformatics.

机构信息

Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun, China.

Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, China.

出版信息

Genet Test Mol Biomarkers. 2020 Sep;24(9):549-561. doi: 10.1089/gtmb.2019.0272. Epub 2020 Jul 31.

DOI:10.1089/gtmb.2019.0272
PMID:32744910
Abstract

Numerous studies, ranging from the alleviation of tissue ischemia to the assessment of cancer prognosis, have demonstrated the fundamental biological differences between human umbilical cord blood-derived endothelial progenitor cells (CB-EPCs) and adult peripheral blood-derived endothelial progenitor cells (PB-EPCs). However, the underlying molecular mechanisms that produce these differences are not clear.The purpose of this study was to identify potential hub genes, key protein interactive networks, and correlated signal pathways unique to CB-EPC biology via bioinformatic methods. We selected the microarray dataset GSE39763 and identified the differentially expressed genes (DEGs) using the "limma" package in the RStudio software. These DEGs were annotated by gene ontology enrichment analyses and signal pathway analyses. A protein-protein interaction (PPI) analysis was then performed to construct PPI networks and identify a hub protein module. We further validated candidate DEGs from the selected module in the gene expression profiling interactive analysis (GEPIA) database because the DEGs were enriched in cancer pathways. Setting an adjusted -value <0.01 and |Log fold change (FC)| ≥ 2 as cutoff criteria, a total of 346 DEGs, including 314 upregulated genes and 32 downregulated genes in CB-EPCs, were identified. Expression of the genes encoding the AT-Hook Containing Transcription Factor 1 (), the Cancer Susceptibility Candidate 5 (), the Centromere Protein C (), the Centromere Protein E (), the Centromere Protein F (), the NUF2 Component of NDC80 Kinetochore Complex (), the RAN-Binding Protein 2 (), the Shugoshin-like 2 (), the Structural Maintenance of Chromosomes 3 (, and the Spindle Apparatus Coiled-Coil Protein 1 () proteins were specifically associated with CB-EPCs. Except for , the other nine genes' expression are all associated with a poorer overall survival rate in cancers. The expression levels of the and genes in tumor patients were significantly higher than those in the controls. The CB-EPCs express genes with greater potential for proliferation and increased migration compared to PB-EPCs; in this regard they are similar to cancer cells.

摘要

大量研究表明,从缓解组织缺血到评估癌症预后,人脐血来源的内皮祖细胞(CB-EPCs)与成人外周血来源的内皮祖细胞(PB-EPCs)之间存在着基本的生物学差异。然而,产生这些差异的潜在分子机制尚不清楚。本研究旨在通过生物信息学方法,确定 CB-EPC 生物学的潜在枢纽基因、关键蛋白互作网络和相关信号通路。我们选择了 microarray 数据集 GSE39763,并使用 RStudio 软件中的“limma”包识别差异表达基因(DEGs)。这些 DEGs 通过基因本体富集分析和信号通路分析进行注释。然后进行蛋白质-蛋白质相互作用(PPI)分析,构建 PPI 网络并识别枢纽蛋白模块。我们进一步在基因表达谱交互分析(GEPIA)数据库中验证所选模块中的候选 DEGs,因为这些 DEGs在癌症途径中富集。设定调整后 P 值<0.01 和 |Log 倍变化(FC)|≥2 为截断标准,共鉴定出 346 个 DEGs,其中 CB-EPCs 中有 314 个上调基因和 32 个下调基因。基因编码的 AT 钩结构域转录因子 1 ()、癌症易感性候选 5 ()、着丝粒蛋白 C ()、着丝粒蛋白 E ()、着丝粒蛋白 F ()、NDC80 动粒复合物的 NUF2 成分 ()、RAN 结合蛋白 2 ()、类苏格肖因 2 ()、染色体 3 的结构维护 () 和纺锤体卷曲螺旋蛋白 1 () 的蛋白表达与 CB-EPCs 特异性相关。除了,其他九个基因的表达都与癌症患者的总体生存率降低相关。肿瘤患者的和基因表达水平明显高于对照组。与 PB-EPCs 相比,CB-EPCs 表达具有更高增殖潜力和迁移能力的基因;在这方面,它们与癌细胞相似。

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