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Research Article

非酒精性脂肪性肝病肝纤维化进展中关键过表达基因的微阵列检测:蛋白质-蛋白质相互作用网络分析

卷 31, 期 23, 2024

发表于: 19 June, 2023

页: [3631 - 3652] 页: 22

弟呕挨: 10.2174/0929867330666230516123028

价格: $65

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摘要

背景：非酒精性脂肪性肝病(NAFLD)是一种常见的慢性肝病，包括单纯性脂肪变性、脂肪性肝炎、纤维化、肝硬化和肝癌等多种疾病。然而，由于NAFLD的全球流行，其中有创性肝活检是诊断的金标准，有必要确定一种更实用的方法来早期诊断NAFLD并提供有用的治疗靶点;因此，分子生物标志物最容易满足这些目标。为此，我们探索了NAFLD患者纤维化进展中的枢纽基因和生物学途径。 方法：从Gene Expression Omnibus数据库下载GEO接入芯片GSE49541的原始数据，应用R包(Affy和Limma)研究低(轻度纤维化0-1分)到高(重度纤维化3-4分)纤维化阶段NAFLD患者的差异表达基因(DEGs)。随后，分析了具有途径富集的显著deg，包括基因本体(GO)、KEGG和Wikipathway。为了进一步探索关键基因，我们建立了蛋白-蛋白相互作用网络(protein-protein interaction network, PPI)，并使用STRING数据库进行可视化，使用Cytoscape和Gephi软件进行进一步分析。进行生存分析以确定中心基因在NAFLD向肝细胞癌进展过程中的总体生存。 结果：共鉴定出311个显著基因，其中高、低组278个表达上调，33个表达下调。这些重要基因的基因功能富集分析表明，它们主要参与细胞外基质(ECM)-受体相互作用、蛋白质消化和吸收以及AGE-RAGE信号通路。PPI网络有196个节点和572条边，PPI富集，p值< 1.0 e-16。基于这个截止点，我们确定了12个基因在四个中心性中得分最高:度、间度、接近度和特征向量。这12个中心基因分别是CD34、THY1、CFTR、COL3A1、COL1A1、COL1A2、SPP1、THBS1、THBS2、LUM、VCAN和VWF。其中四个枢纽基因，即CD34、VWF、SPP1和VCAN，与肝细胞癌的发展有显著的相关性。 结论：这项对deg的PPI网络分析确定了参与纤维化进展的关键枢纽基因，以及它们在NAFLD患者中发挥作用的生物学途径。这12个基因为进一步集中研究确定治疗应用的潜在靶点提供了极好的机会。

关键词: 基因表达，Wikipathway, KEGG富集，GO本体，PPI网络，枢纽基因，生存分析。

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