Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism [Set1]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE48000 | GEO | 2015/11/23
SECONDARY ACCESSION(S): PRJNA208790
REPOSITORIES: GEO
Similar Datasets
Project description:Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. We studied 134 patients with VTE separated into 3 groups: (1) âlow-riskâ patients had â¥1 provoked VTE; (2) âmoderate-riskâ patients had no more than 1 unprovoked VTE; (3) âhigh-riskâ patients had â¥2 unprovoked VTE. 44 individuals with no history of VTE were enrolled as healthy controls. Consented individuals were enrolled at 4 medical centers in the US. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Using class prediction analysis, we distinguished high-risk patients from healthy controls with good receiver operating curve characteristics (AUC=0.88). We also distinguished high-risk from low-risk individuals, moderate-risk individuals from healthy controls, and low-risk individuals from healthy controls with AUCâs of 0.72, 0.77 and 0.72, respectively. Using differential expression analysis, we identified genes relevant to coagulation, immune response and vascular biology, such as SELP and CD46, which were differentially expressed in at least two comparisons. Neither approach distinguished the moderate-risk patients from the high-risk or low-risk groups. Gene expression profiles may provide insights into biological mechanisms associated with patients at risk for recurrent VTE. Prospective studies are needed to validate these findings. This study includes a total of 218 samples/individuals (in 5 groups; APS, high-risk VTE, moderate-risk VTE, low-risk VTE and healthy-controls). Samples in which the percent of probes present was 15% or less (n=51) were excluded leaving 167 samples. The data for these 167 samples were normalized together. However, this record represents the 132 individual samples in the following groups; high-risk (n=40); moderate-risk (n=33); low-risk (n=34); and healthy controls (n=25). The 35 samples in APS group are represented in GSE48001.
2015-11-23 | E-GEOD-48000 | biostudies-arrayexpress
Project description:Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Pulmonary embolism is a life threatening manifestation of VTE that occurs in at least half the patients on presentation. In addition, VTE recurs in up to 30% of patients after a standard course of anticoagulation, and there is not a reliable way of predicting recurrence. We investigated whether gene expression profiles of whole blood could distinguish patients with VTE from healthy controls, single VTE from those with recurrence, and DVT alone from those with PE. 70 adults with VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays. We developed a 50 gene model that distinguished healthy controls from subjects with VTE with excellent receiver operating characteristics (AUC 0.94; P < 0.0001). We also discovered a separate 50 gene model that distinguished subjects with a single VTE from those with recurrent VTE with good receiver operating characteristics (AUC 0.75; P=0.008). In contrast, we were unable to distinguish subjects with DVT from those with PE using gene expression profiles. Gene expression profiles of whole blood can distinguish subjects with VTE from healthy controls and subjects with a single VTE from those with recurrence. Additional studies should be performed to validate these results and develop diagnostic tests. Gene expression profiling is likely translatable to other thrombotic disorders(e.g., patients with cancer and VTE).
2011-11-10 | GSE19151 | GEO
Project description:Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Pulmonary embolism is a life threatening manifestation of VTE that occurs in at least half the patients on presentation. In addition, VTE recurs in up to 30% of patients after a standard course of anticoagulation, and there is not a reliable way of predicting recurrence. We investigated whether gene expression profiles of whole blood could distinguish patients with VTE from healthy controls, single VTE from those with recurrence, and DVT alone from those with PE. 70 adults with VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays. We developed a 50 gene model that distinguished healthy controls from subjects with VTE with excellent receiver operating characteristics (AUC 0.94; P < 0.0001). We also discovered a separate 50 gene model that distinguished subjects with a single VTE from those with recurrent VTE with good receiver operating characteristics (AUC 0.75; P=0.008). In contrast, we were unable to distinguish subjects with DVT from those with PE using gene expression profiles. Gene expression profiles of whole blood can distinguish subjects with VTE from healthy controls and subjects with a single VTE from those with recurrence. Additional studies should be performed to validate these results and develop diagnostic tests. Gene expression profiling is likely translatable to other thrombotic disorders(e.g., patients with cancer and VTE). 70 adults with one or more prior VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays.
2011-11-10 | E-GEOD-19151 | biostudies-arrayexpress
Project description:Background: Patients with high-grade gliomas are at high risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) are small non-coding RNAs with multiple roles in tumor biology, hemostasis and platelet function. We aimed to explore the association between plasma miRNAs and risk of VTE in high-grade glioma. Results: We conducted a nested-case control study within 152 patients with WHO grade IV glioma that had been included in the Vienna Cancer and Thrombosis Study (CATS), a prospective cohort study focused on risk factors for VTE in newly diagnosed or recurrent cancer. At study inclusion a single blood draw was taken, and patients were thereafter followed for a maximum of two years. During that time, 24 patients (16%) developed VTE. Of the other 128 patients, we randomly selected 24 age- and sex-matched controls. After sample quality control, the final group size was 21 VTE-patients and 23 without VTE. Small RNA next-generation sequencing of plasma was performed. We observed that hsa-miR-451a was globally the most abundant miRNA. Notably, 51% of all miRNAs showed a correlation with platelet count. The analysis of miRNAs differentially regulated in VTE patients – with and without platelet adjustment – identified potential VTE biomarker candidates such as has-miR- 221-3p. Conclusion: We here provide one of the largest and deepest peripheral blood miRNA datasets of high-grade glioma patients so far. Further, we confirm previous observations of a considerable impact of platelet count on the blood miRNome. And, finally, we present first VTE biomarker candidates that can serve as the starting point for future confirmatory research.
2023-12-31 | GSE222666 | GEO
Project description:Younger age and VTE recurrence are more likely to be caused by genetic risk factors than secondary VTE in older patients who more likely have comorbidities. When the exome rare variant genotyping database of the Scripps VTE Registry for adults < 55 yrs old was generated and analyzed for single nucleotide polymorphisms (SNPs). Two F5 related SNPs (rs6025, factor V Leiden and rs6687813) exceeded significance (FDR (false discovery rate) p < 0.05). No other variants met genome-wide significance. When the data for the subgroup of cases with recurrent VTE that are more likely to have genetic risk factors than cases with a single VTE episode were compared to controls (N=211 controls and N=32 recurrent VTE cases), 28 SNPs, including the F5 rs6025 SNP, achieved significance (FDR p < 0.05).
2021-12-04 | GSE76016 | GEO
Project description:Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We use multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, to identify Complement Factor H Related Protein 5 (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
2023-03-25 | PXD040913 | Pride
Project description:Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. The unfavorable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported both in thrombotic APS and venous thromboembolism (VTE). The presence and amount of different proteins within a plasma clot, not only associated with the coagulation system, may influence clot properties. To our knowledge, there is a lack of data on plasma fibrin-clot bound proteins in patients with thrombotic APS or VTE. The aim of our study was to perform a quantitative proteomic analysis of fibrin clots prepared from citrated plasma from subjects with thrombotic APS and prior VTE, along with fibrin clot permeability (Ks) and clot lysis time (CLT) assessed ex vivo. We investigated 23 consecutive patients with APS, 18 with a history of first-ever VTE, and 20 age and sex matched healthy subjects. A multiple enzyme digestion filter aided sample preparation and a multienzyme digestion (MED) FASP method combined with LC-MS/MS analysis performed on a Proxeon Easy-nLC System coupled to the Q Exactive HF mass spectrometer were used. The proteomic analysis revealed that clot composition regarding 117 proteins in APS patients and 48 proteins in VTE patients was changed as compared to healthy controls, while 72 clot-bounded proteins differed between APS and VTE subjects. In healthy controls, Ks was associated with fibrinogen alpha and gamma chains (r=0.46 and r=0.46, both p<0.05, respectively) or apolipoprotein B-100 (r=-0.53, p<0.05), while CLT correlated with annexin A2 (r=-0.58, p<0.05), apolipoportein(a) (r=0.47, p<0.05), or platelet glycoprotein 4 (r=0.59, p<0.05). In VTE patients correlations of Ks with complement C1q and histone H2B, as factors closely linked with thrombosis, were observed (r=-0.52 and r=-0.47, both p<0.05, respectively). In patients with thrombotic APS all above-mentioned associations were not found. This study is the first to show that different proteins are able to influence the clot formation, structure, and properties. Since, prothrombotic conditions abolished associations observed in healthy subjects fibrin clots, differences in protein clot components might explain the links between prothrombotic fibrin clot phenotype and thromboembolic events.
2019-08-20 | PXD008434 | Pride
Project description:Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a main cause of morbidity and mortality that causes tremendous health care costs. Short term immobility related conditions arising from hospitalization, acute trauma and forced bed rest are major risk factors for the development of VTE. In contrast, chronically paralyzed patients with post-spinal cord injury are protected from VTE despite immobilization. Similarly, free-ranging brown bears (Ursus arctos) that hibernate (immobilize) have adapted to this threat through yet to be discovered mechanisms and do not develop VTE. This suggests that long-term immobility can induce antithrombotic mechanisms that are evolutionarily conserved. Here we aimed to identify these adaptive mechanisms of VTE protection in a cross-species approach. Mass spectrometry-based proteomics identified platelet expressed heat shock protein 47 (Hsp47) as the most substantially downregulated protein during brown bear hibernation. In a clinical bed rest study and in spinal-cord injured humans, we likewise observed drastic reduction of platelet-expressed Hsp47. Genetic ablation and pharmaceutical inhibition of platelet Hsp47 attenuates deep vein thrombosis and thromboinflammatory responses in mice and human blood cells. This suggests that Hsp47 downregulation is an evolutionarily conserved mechanism that also protects immobilized patients from VTE. Our translational approach thus identified an antithrombotic signature that may give rise to novel antithrombotic therapeutics and prognostic markers.
2023-04-14 | PXD031521 | Pride
Project description:Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a main cause of morbidity and mortality that causes tremendous health care costs. Short term immobility related conditions arising from hospitalization, acute trauma and forced bed rest are major risk factors for the development of VTE. In contrast, chronically paralyzed patients with post-spinal cord injury are protected from VTE despite immobilization. Similarly, free-ranging brown bears (Ursus arctos) that hibernate (immobilize) have adapted to this threat through yet to be discovered mechanisms and do not develop VTE. This suggests that long-term immobility can induce antithrombotic mechanisms that are evolutionarily conserved. Here we aimed to identify these adaptive mechanisms of VTE protection in a cross-species approach. Mass spectrometry-based proteomics identified platelet expressed heat shock protein 47 (Hsp47) as the most substantially downregulated protein during brown bear hibernation. In a clinical bed rest study and in spinal-cord injured humans, we likewise observed drastic reduction of platelet-expressed Hsp47. Genetic ablation and pharmaceutical inhibition of platelet Hsp47 attenuates deep vein thrombosis and thromboinflammatory responses in mice and human blood cells. This suggests that Hsp47 downregulation is an evolutionarily conserved mechanism that also protects immobilized patients from VTE. Our translational approach thus identified an antithrombotic signature that may give rise to novel antithrombotic therapeutics and prognostic markers.
2023-04-14 | PXD039087 | Pride
Project description:Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a main cause of morbidity and mortality that causes tremendous health care costs. Short term immobility related conditions arising from hospitalization, acute trauma and forced bed rest are major risk factors for the development of VTE. In contrast, chronically paralyzed patients with post-spinal cord injury are protected from VTE despite immobilization. Similarly, free-ranging brown bears (Ursus arctos) that hibernate (immobilize) have adapted to this threat through yet to be discovered mechanisms and do not develop VTE. This suggests that long-term immobility can induce antithrombotic mechanisms that are evolutionarily conserved. Here we aimed to identify these adaptive mechanisms of VTE protection in a cross-species approach. Mass spectrometry-based proteomics identified platelet expressed heat shock protein 47 (Hsp47) as the most substantially downregulated protein during brown bear hibernation. In a clinical bed rest study and in spinal-cord injured humans, we likewise observed drastic reduction of platelet-expressed Hsp47. Genetic ablation and pharmaceutical inhibition of platelet Hsp47 attenuates deep vein thrombosis and thromboinflammatory responses in mice and human blood cells. This suggests that Hsp47 downregulation is an evolutionarily conserved mechanism that also protects immobilized patients from VTE. Our translational approach thus identified an antithrombotic signature that may give rise to novel antithrombotic therapeutics and prognostic markers.
2023-04-14 | PXD030465 | Pride