Abstract

BackgroundThe pathogenic mechanisms of venous thromboembolism (VT) remain to be defined. This study aimed to identify differentially expressed genes (DEGs) that could serve as potential therapeutic targets for VT.MethodsTwo human datasets (GSE19151 and GSE48000) were analyzed by the robust rank aggregation method. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were conducted for the DEGs. To explore potential correlations between gene sets and clinical features and to identify hub genes, we utilized weighted gene coexpression network analysis (WGCNA) to build gene coexpression networks incorporating the DEGs. Then, the levels of the hub genes were analyzed in the GSE datasets. Based on the expression of the hub genes, the possible pathways were explored by gene set enrichment analysis and gene set variation analysis. Finally, the diagnostic value of the hub genes was assessed by receiver operating characteristic (ROC) analysis in the GEO database.ResultsIn this study, we identified 54 upregulated and 10 downregulated genes that overlapped between normal and VT samples. After performing WGCNA, the magenta module was the module with the strongest negative correlation with the clinical characteristics. From the key module, FECH, GYPA, RPIA and XK were chosen for further validation. We found that these genes were upregulated in VT samples, and high expression levels were related to recurrent VT. Additionally, the four hub genes might be highly correlated with ribosomal and metabolic pathways. The ROC curves suggested a diagnostic value of the four genes for VT.ConclusionsThese results indicated that FECH, GYPA, RPIA and XK could be used as promising biomarkers for the prognosis and prediction of VT.

Highlights

  • Venous thromboembolism (VT), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), has been reported to be the third most commonlyFan et al BMC Cardiovascular Disorders (2021) 21:577In recent decades, considerable attention has been given to exploring new biomarkers and potential molecular mechanisms for venous thromboembolism (VT) diagnosis and therapy [7,8,9,10]

  • This is a noteworthy finding, as it suggests that the PAI-1 4G/5G polymorphism might be a prospective VT risk biomarker, especially in the Asian population, according to a meta-analysis [11]

  • We found that the significance of the yellow, green–yellow, pink, and magenta modules was higher than that of the others module, implying that these modules might have a significant relationship with VT (Fig. 4e)

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Summary

Introduction

Venous thromboembolism (VT), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), has been reported to be the third most commonlyFan et al BMC Cardiovascular Disorders (2021) 21:577In recent decades, considerable attention has been given to exploring new biomarkers and potential molecular mechanisms for VT diagnosis and therapy [7,8,9,10]. Based on the GEO database, RPL9, RPL5, RPS20, TP53, and RPL23 were enriched in the ribosome pathway, validating them as potential targets for VT therapy [9]. This is a noteworthy finding, as it suggests that the PAI-1 4G/5G polymorphism might be a prospective VT risk biomarker, especially in the Asian population, according to a meta-analysis [11]. We identified the four hub genes FECH, GYPA, RPIA, and XK as new biomarkers and verified the prognostic and predicted values for VT patients. This study aimed to identify differentially expressed genes (DEGs) that could serve as potential therapeutic targets for VT

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