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Identification of biomarkers of venous thromboembolism by bioinformatics analyses.

ABSTRACT: Venous thromboembolism (VTE) is a common vascular disease and a major cause of mortality. This study intended to explore the biomarkers associated with VTE by bioinformatics analyses.Based on Gene Expression Omnibus (GEO) database, the GSE19151 expression profile data were downloaded. The differentially expressed genes (DEGs) between single VTE (sVTE)/recurrent VTE (rVTE) and control were identified. Then, pathway enrichment analysis of DEGs were performed, followed by protein-protein interaction (PPI) network construction.Total 433 upregulated and 222 downregulated DEGs were obtained between sVTE and control samples. For rVTE versus control, 625 upregulated and 302 downregulated DEGs were identified. The overlap DEGs were mainly enriched in the pathways related to ribosome, cancer, and immune disease. The DEGs specific to rVTE were enriched in several pathways, such as nod-like receptor signaling pathway. In the PPI network, 2 clusters of VTE genes, including ribosomal protein family genes and NADH family-ubiquinol-cytochrome genes, were identified, such as ribosomal protein L9 (RPL9), RPL5, RPS20, RPL23, and tumor protein p53 (TP53).The nod-like receptor signaling pathway, ribosomal protein family genes, such as RPL9, RPL5, RPS20, and RPL23, and DEG of TP53 may have the potential to be used as targets for diagnosis and treatment of VTE.

SUBMITTER: Wang G

PROVIDER: S-EPMC5902267 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Identification of biomarkers of venous thromboembolism by bioinformatics analyses.

Wang Guiming G Zhao Wenbo W Yang Yudong Y Yang Gaochao G Wei Zhigang Z Guo Jiansheng J

Medicine 20180401 14

Venous thromboembolism (VTE) is a common vascular disease and a major cause of mortality. This study intended to explore the biomarkers associated with VTE by bioinformatics analyses.Based on Gene Expression Omnibus (GEO) database, the GSE19151 expression profile data were downloaded. The differentially expressed genes (DEGs) between single VTE (sVTE)/recurrent VTE (rVTE) and control were identified. Then, pathway enrichment analysis of DEGs were performed, followed by protein-protein interactio ...[more]

PMID: 29620629

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Project description:Background:Cholangiocarcinoma (CCA) is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. Methods:The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. Results:Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients. Conclusions:CASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.

Project description:IntroductionDespite evidence-based guidelines for venous thromboembolism prevention, substantial variability is found in practice. Many economic evaluations of new drugs for thromboembolism prevention do not occur prospectively with efficacy studies and are sponsored by the manufacturers, raising the possibility of bias. We performed a systematic review of economic analyses of venous thromboembolism prevention in hospitalized patients to inform clinicians and policy makers about cost-effectiveness and the potential influence of sponsorship.MethodsWe searched MEDLINE, EMBASE, Cochrane Databases, ACP Journal Club, and Database of Abstracts of Reviews of Effects, from 1946 to September 2011. We extracted data on study characteristics, quality, costs, and efficacy.ResultsFrom 5,180 identified studies, 39 met eligibility and quality criteria. Each addressed pharmacologic prevention: low-molecular-weight heparins versus placebo (five), unfractionated heparin (12), warfarin (eight), one or another agents (five); fondaparinux versus enoxaparin (11); and rivaroxaban and dabigatran versus enoxaparin (two). Low-molecular-weight heparins were most economically attractive among most medical and surgical patients, whereas fondaparinux was favored for orthopedic patients. Fondaparinux was associated with increased bleeding events. Newer agents rivaroxaban and dabigatran may offer additional value. Of all economic evaluations, 64% were supported by manufacturers of a "new" agent. The new agent had a favorable outcome in 38 (97.4%) of 39 evaluations [95% confidence interval [CI] (86.5 to 99.9)]. Among studies supported by a pharmaceutical company, the sponsored medication was economically attractive in 24 (96.0%) of 25 [95% CI, 80.0 to 99.9)]. We could not detect a consistent bias in outcome based on sponsorship; however, only a minority of studies were unsponsored.ConclusionLow-molecular-weight heparins and fondaparinux are the most economically attractive drugs for venous thromboembolism prevention in hospitalized patients. Approximately two thirds of evaluations were supported by the manufacturer of the new agent; such drugs were likely to be reported as economically favorable.

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Identification of biomarkers of venous thromboembolism by bioinformatics analyses.

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Identification of biomarkers of venous thromboembolism by bioinformatics analyses.

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