Pulmonary arterial hypertension (PAH) is a life-threatening condition. The aim of this study was to explore potential crucial genes and pathways associated with PAH based on integrative analyses of gene expression and to shed light on the identification of biomarker for PAH. Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). After the identification of differentially expressed genes (DEGs), hub pathways and genes were identified based on the comprehensive evaluation of protein-protein interaction (PPI) network analysis, modular analysis and cytohubba’s analysis, and further validated in another PAH transcriptomic dataset (GSE33463). Potentially associated micro-RNAs (miRNAs) were also predicted. A total of 521 DEGs were found between PAH and normal controls, including 432 up-regulated DEGs and 89 down-regulated DEGs. Functional enrichment analysis showed that these DEGs were mainly enriched in mitotic cell cycle process, mitotic cell cycle and microtubule cytoskeleton organization. Moreover, five key genes (CDK1, SMC2, SMC4, KIF23, and CENPE) were identified and then further validated in another transcriptomic dataset associated with special phenotypes of PAH. Furthermore, these hub genes were mainly enriched in promoting mitotic cell cycle process, which may be closely associated with the pathogenesis of PAH. We also found that the predicted miRNAs targeting these hub genes were found to be enriched in TGF-β and Hippo signaling pathway. These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

中文翻译：

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基因表达谱的综合分析揭示了有丝分裂细胞周期和微管细胞骨架在肺动脉高压中的潜在关键作用。

肺动脉高压（PAH）是威胁生命的疾病。这项研究的目的是基于基因表达的综合分析，探索与PAH相关的潜在关键基因和途径，并为PAH的生物标记物鉴定提供启示。从公共数据库（GSE53408和GSE113439）下载了来自27位PAH患者和22位正常对照的肺组织的基因表达谱。鉴定出差异表达基因（DEG）后，基于对蛋白质-蛋白质相互作用（PPI）网络分析，模块分析和cytohubba分析的综合评估，鉴定了枢纽途径和基因，并在另一个PAH转录组数据集中（GSE33463）进行了验证。还预测了潜在相关的微小RNA（miRNA）。在PAH和正常对照之间共发现521个DEG，包括432个上调的DEG和89个下调的DEG。功能富集分析表明，这些DEG主要富集在有丝分裂细胞周期过程，有丝分裂细胞周期和微管细胞骨架组织中。此外，确定了五个关键基因（CDK1，SMC2，SMC4，KIF23和CENPE），然后在另一个与PAH特殊表型相关的转录组数据集中进行了验证。此外，这些中枢基因主要在促进有丝分裂细胞周期过程中富集，这可能与PAH的发病机理密切相关。我们还发现，靶向这些中枢基因的预测miRNA被发现富含TGF-β和Hippo信号通路。