Identification of novel biomarkers involved in pulmonary arterial hypertension based on multiple-microarray analysis

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disorder. However, studies providing PAH-related gene expression profiles are scarce. To identify hub genes involved in PAH, we investigate two microarray data sets from gene expression omnibus (GEO). A total of 150 differentially expressed genes (DEGs) were identified by limma package. Enriched Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included mitotic nuclear division, ATPase activity, and Herpes simplex virus one infection. Ten hub genes from three significant modules were ascertained by Cytoscape (CytoHubba). Gene set enrichment analysis (GSEA) plots showed that transcription elongation factor complex was the most significantly enriched gene set positively correlated with the PAH group. At the same time, solute proton symporter activity was the most significantly enriched gene set positively correlated with the control group. Correlation analysis between hub genes suggested that SMC4, TOP2A, SMC2, KIF11, KIF23, ANLN, ARHGAP11A, SMC3, SMC6 and RAD50 may involve in the pathogenesis of PAH. Then, the miRNA-target genes regulation network was performed to unveil the underlying complex association among them. Finally, RNA extracted from monocrotaline (MCT)-induced Rat-PAH model lung artery tissues were to conduct quantitative real-time PCR (qRT-PCR) to validate these hub genes. In conclusion, our study offers new evidence for the underlying molecular mechanisms of PAH as well as attractive targets for diagnosis and treatment of PAH.

Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension

“…It hypothesizes that each gene is randomly ordered, if a gene is upregulated or downregulated in all gene lists, then the gene is considered robust ( 9 ). Up to now, there have been several studies that integrated PAH datasets adopting batch normalization method for consolidation while there are rare studies using RRA method for data integration ( 10 , 11 ), which facilitated this study.…”

Molecular Characterization and Elucidation of Pathways to Identify Novel Therapeutic Targets in Pulmonary Arterial Hypertension

“…Similarly, SMC4 is a vital core subunit of condensin, which has an essential impact on mitotic chromosome condensation (Takemoto et al, 2004;Luo et al, 2020). It has been suggested that knockdown of SMC4 could inhibit Toll-like receptor-mediated production of several proinflammatory cytokines, including IL-6 and TNF-α in macrophages (Ma et al, 2020). Interaction of EEA1 with plateletderived growth factor receptor can mark early endosomes, which are required for the progression of secondary pulmonary alveolar septa, which reflected that the internalization of TGF-R by clathrin-mediated endocytosis in EEA1-positive endosomes resulted in productive nuclear signaling via the interaction of TGF-R with Smad anchor for receptor activation (SARA) (Saker et al, 2016;Chrifi et al, 2019).…”

“…The wide application of cardiac catheterization and echocardiography in clinical practice, evaluation of pulmonary artery pressure and right heart hemodynamic as well as high-resolution image data are no longer difficult to access, which significantly improve the differential diagnosis and assessment of patients with PAH (Claessen and La Gerche, 2017;Farhadi et al, 2017). Indeed, there is tremendous progress in understanding the essential pathophysiology of PAH, including the prognostic biomarkers as well as many promising therapy options (Ma et al, 2020). However, there are limited studies providing PAH-associated gene expression profiles, and a number of studies implying that there may be an extraordinary significance of investigating this type of clinical molecular biomarkers and elucidating the fundamental mechanisms involved in PAH.…”

“…However, there are limited studies providing PAH-associated gene expression profiles, and a number of studies implying that there may be an extraordinary significance of investigating this type of clinical molecular biomarkers and elucidating the fundamental mechanisms involved in PAH. This may be useful in developing a new scientific-based diagnosis modality and performing targeted therapy in patients with PAH more precisely (Farhadi et al, 2017;Sullivan and Kass, 2019;Ma et al, 2020;Maremanda et al, 2020).…”

Analysis of Sepsis Markers and Pathogenesis Based on Gene Differential Expression and Protein Interaction Network

“…It has been widely applied to identify hub genes of diseases at the molecular level. Many bioinformatics studies on other diseases have been carried out, such as acute kidney injury [ 3 ], Alzheimer's disease [ 4 ], and pulmonary arterial hypertension [ 5 ], and important progress has been made, and disease-related differentially expressed genes have been obtained.…”