动脉性肺动脉高压特异性差异表达基因的筛选及生物信息学分析-现代医学

动脉性肺动脉高压特异性差异表达基因的筛选及生物信息学分析

单位：南京医科大学附属无锡人民医院/南京医科大学无锡医学中心肺移植中心, 江苏无锡 214023

分类号：R563;R363.2

出版年·卷·期（页码）：2023·51·第十二期（1697-1704）

摘要：

目的：筛选动脉性肺动脉高压(PAH)相关的特异性差异表达基因，了解相关生物学功能，为进一步寻找PAH潜在调控靶点提供理论依据。方法：从美国国立生物技术信息中心的基因表达数据库(GEO)下载GSE117261和GSE113439高通量基因表达数据集。筛查PAH患者和对照人群的差异表达基因。利用“WGCNA”包进行加权基因共表达网络分析(WGCNA)以鉴定PAH表型特异性基因。将两者重叠部分定义为PAH特异性差异表达基因。并通过基因本体(gene ontology, GO)及京都基因和基因组百科全书(KEGG)分析进一步探索其潜在的生物学功能。此外，通过构建蛋白质-蛋白质交互作用(PPI)网络，以识别枢纽基因。结果：共获得414个差异表达基因，其中230个基因显著上调，184个基因显著下调。MEmidnightblue模块中919个基因为PAH表型特异性基因。确定了其交集的135个基因为PAH特异性差异表达基因。GO和KEGG分析表明，差异表达基因主要涉及细胞增殖、细胞趋化和炎症反应等生物学过程。基于PPI网络，将POSTN、ILR2、ILR4、CD163、KIT鉴定为枢纽基因。结论：POSTN、ILR2、ILR4、CD163、KIT可能是参与PAH发生的特异性差异表达基因，这为探寻潜在生物标志物和药物靶点提供了理论基础。

Objective: To screen specific differentially expressed genes in the occurrence of pulmonary arterial hypertension(PAH) and understand the related biological functions, so as to provide theoretical basis for further exploration of potential regulatory targets of PAH. Methods: High-throughput gene expression datasets GSE117261 and GSE113439 were download from the gene expression omnibus(GEO) of the National Center for Biotechnology Information in the United States.The differentially expressed genes were identified by screening PAH patients and controls.Then, the “WGCNA” package was used for weighted gene co-expression network analysis(WGCNA) to identify PAH phenotypic specific genes.The overlap was defined as PAH specific differentially expressed genes.The potential biological functions were further explored through gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis.In addition, a protein-protein interaction(PPI) networks were constructed to identify hub genes. Results: A total of 414 differentially expressed genes were obtained, of which 230 genes were significantly up regulated and 184 genes were significantly downregulated. The 919 genes in the MEmidnightblue module were PAH phenotypic specific genes.The 135 genes that intersect were identified as PAH specific differentially expressed genes.GO and KEGG analysis showed that these genes were mainly involved in biological processes such as cell proliferation, cell chemotaxis, and inflammatory response.In view of PPI network, POSTN,ILR2,ILR4,CD163 and KIT were identified as hub genes. Conclusion: POSTN， ILR2， ILR4， CD163 and KIT may be specific differentially expressed genes involved in the occurrence of PAH, which provides a theoretical basis for exploring potential biomarkers and drug targets.

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