Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension

Jing Luo,Chenlu Li,Saisai Lu,Xiaochun Zhu,Jing Guo,Zhenwei Liu,Jinxia Fang,Haiyan Li,Ruochen Wang,Xiaobing Wang

doi:10.1186/s12920-020-00740-x

Abstract

BackgroundPulmonary 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.MethodsGene 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.ResultsA 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.ConclusionThese findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

Highlights

Pulmonary arterial hypertension (PAH) is a life-threatening condition
According to latest classification criteria, PAH can be divided into idiopathic PAH (IPAH), heritable PAH, drug- and toxin-induced PAH, PAH associated with other disease and so on [3]
[logFC] > 1), 521 differentially expressed genes (DEGs) between PAH and normal controls were identified, including 432 up-regulated genes and 89 down-regulated genes displayed by volcano plot (Fig. 1b and Table S2)

Summary

Introduction

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. PAH is defined based on the elevation of the mean pulmonary arterial pressure (mPAP) above 25 mmHg at resting state and a pulmonary vascular resistance > 3 Wood units, as well as a pulmonary capillary wedge pressure (PCWP) < 15 mmHg at end expiration [2] This 6th World Symposium on Pulmonary Hypertension (WSPH) Task Force proposed to define the low limit of mPAP for PAH to be 20 mmHg [3] The increase in afterload puts great stress on the right ventricle (RV), leading to RV hypertrophy, and RV failure and death [4]. Revealing the causes and underlying molecular mechanisms of the disease, as well as discovering molecular biomarkers for early diagnosis, prevention and personalized treatment, is especially important and highly demanded for PAH

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