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

Abstract

Background: Pulmonary arterial hypertension (PAH) is a life-threatening condition that gets worse over time. Despite advances in the development of strategies for treating PAH, prognosis of the disease remains unsatisfactory, especially for advanced PAH. The aim of this study was to explore potential crucial genes and pathways associated with PAH based on integrative analyses of gene expression and shed light on the identification of biomarker for PAH. Results: Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). A total of 521 differentially expressed genes (DEGs), including 432 up-regulated DEGs and 89 down-regulated DEGs were identified using “limma” package in R. 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 based on the comprehensive evaluation of protein-protein interaction (PPI) network analysis, modular analysis and cytohubba’s analysis, then further validated in another transcriptomic data set associated with PAH from public database (GSE33463). 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 micro-RNAs (miRNAs) targeting these hub genes were found to be enriched in TGF-β and Hippo signaling pathway. Conclusion:These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.