Identification of differentially expressed genes present in the whole blood of Pulmonary Arterial Hypertension patients and control patients: An integrated bioinformatics approach

Ezenwa, Chisom; Soremekun, Opeyemi; Nashiru, Oyekanmi; Fatumo, Segun

doi:10.1016/j.imu.2020.100380

Cited by 2 publications

(1 citation statement)

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“…A whole-blood RNA signature of PAH is associated with disease severity and correlated with poor clinical outcomes in patients ( Rhodes et al, 2020 ). Blood-derived transcriptomes are related to the signaling pathways and gene ontology involved with the pathogenesis and progression of PAH ( Ezenwa et al, 2020 ). These previous studies show that transcriptomic analysis is crucial to identifying the substantial molecular regulators in PAH patients.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis and validation of novel immune and vascular remodeling related genes signature associated with drug interactions in pulmonary arterial hypertension

et al. 2022

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Background: Previous studies revealed that the gene signatures are associated with the modulation and pathogenesis of pulmonary arterial hypertension (PAH). However, identifying critical transcriptional signatures in the blood of PAH patients remains lacking.Methods: The differentially expressed transcriptional signatures in the blood of PAH patients were identified by a meta-analysis from four microarray datasets. Then we investigated the enrichment of gene ontology and KEGG pathways and identified top hub genes. Besides, we investigated the correlation of crucial hub genes with immune infiltrations, hallmark gene sets, and blood vessel remodeling genes. Furthermore, we investigated the diagnostic efficacy of essential hub genes and their expression validation in an independent cohort of PAH, and we validate the expression level of hub genes in monocrotaline (MCT) induced PAH rats’ model. Finally, we have identified the FDA-approved drugs that target the hub genes and their molecular docking.Results: We found 1,216 differentially expressed genes (DEGs), including 521 up-regulated and 695 down-regulated genes, in the blood of the PAH patients. The up-regulated DEGs are significantly associated with the enrichment of KEGG pathways mainly involved with immune regulation, cellular signaling, and metabolisms. We identified 13 master transcriptional regulators targeting the dysregulated genes in PAH. The STRING-based investigation identified the function of hub genes associated with multiple immune-related pathways in PAH. The expression levels of RPS27A, MAPK1, STAT1, RPS6, FBL, RPS3, RPS2, and GART are positively correlated with ssGSEA scores of various immune cells as positively correlated with the hallmark of oxidative stress. Besides, we found that these hub genes also regulate the vascular remodeling in PAH. Furthermore, the expression levels of identified hub genes showed good diagnostic efficacy in the blood of PAH, and we validated most of the hub genes are consistently dysregulated in an independent PAH cohort. Validation of hub genes expression level in the monocrotaline (MCT)-induced lung tissue of rats with PAH revealed that 5 screened hub genes (MAPK1, STAT1, TLR4, TLR2, GART) are significantly highly expressed in PAH rats, and 4 screened hub genes (RPS6, FBL, RPS3, and RPS2) are substantially lowly expressed in rats with PAH. Finally, we analyzed the interaction of hub proteins and FDA-approved drugs and revealed their molecular docking, and the results showed that MAPK1, TLR4, and GART interact with various drugs with appropriate binding affinity.Conclusion: The identified blood-derived key transcriptional signatures significantly correlate with immune infiltrations, hypoxia, glycolysis, and blood vessel remodeling genes. These findings may provide new insight into the diagnosis and treatment of PAH patients.

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Section: Introductionmentioning

confidence: 99%