Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism

Deborah A. Lewis, Sunil Suchindran, Michele G. Beckman, W. Craig Hooper, Althea M. Grant, John A. Heit, Marilyn Manco-Johnson, Stephan Moll, Claire S. Philipp, Kristy Kenney, Christine De Staercke, Meredith E. Pyle, Jen Tsan Chi, Thomas L. Ortel

Research output: Contribution to journalArticle

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Abstract

Introduction Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. Objectives To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/Methods We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had 2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Results Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. Conclusion Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.

Original languageEnglish (US)
Pages (from-to)659-665
Number of pages7
JournalThrombosis Research
Volume135
Issue number4
DOIs
StatePublished - Apr 1 2015

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Venous Thromboembolism
Transcriptome
Phenotype
Area Under Curve
Genes
Inborn Genetic Diseases
ROC Curve
Genome
RNA

Keywords

  • deep-vein thrombosis
  • gene expression profiling
  • venous thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Lewis, D. A., Suchindran, S., Beckman, M. G., Hooper, W. C., Grant, A. M., Heit, J. A., ... Ortel, T. L. (2015). Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism. Thrombosis Research, 135(4), 659-665. https://doi.org/10.1016/j.thromres.2015.02.003

Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism. / Lewis, Deborah A.; Suchindran, Sunil; Beckman, Michele G.; Hooper, W. Craig; Grant, Althea M.; Heit, John A.; Manco-Johnson, Marilyn; Moll, Stephan; Philipp, Claire S.; Kenney, Kristy; De Staercke, Christine; Pyle, Meredith E.; Chi, Jen Tsan; Ortel, Thomas L.

In: Thrombosis Research, Vol. 135, No. 4, 01.04.2015, p. 659-665.

Research output: Contribution to journalArticle

Lewis, DA, Suchindran, S, Beckman, MG, Hooper, WC, Grant, AM, Heit, JA, Manco-Johnson, M, Moll, S, Philipp, CS, Kenney, K, De Staercke, C, Pyle, ME, Chi, JT & Ortel, TL 2015, 'Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism', Thrombosis Research, vol. 135, no. 4, pp. 659-665. https://doi.org/10.1016/j.thromres.2015.02.003
Lewis, Deborah A. ; Suchindran, Sunil ; Beckman, Michele G. ; Hooper, W. Craig ; Grant, Althea M. ; Heit, John A. ; Manco-Johnson, Marilyn ; Moll, Stephan ; Philipp, Claire S. ; Kenney, Kristy ; De Staercke, Christine ; Pyle, Meredith E. ; Chi, Jen Tsan ; Ortel, Thomas L. / Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism. In: Thrombosis Research. 2015 ; Vol. 135, No. 4. pp. 659-665.
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abstract = "Introduction Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30{\%} of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. Objectives To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/Methods We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had 2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Results Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. Conclusion Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.",
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T1 - Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism

AU - Lewis, Deborah A.

AU - Suchindran, Sunil

AU - Beckman, Michele G.

AU - Hooper, W. Craig

AU - Grant, Althea M.

AU - Heit, John A.

AU - Manco-Johnson, Marilyn

AU - Moll, Stephan

AU - Philipp, Claire S.

AU - Kenney, Kristy

AU - De Staercke, Christine

AU - Pyle, Meredith E.

AU - Chi, Jen Tsan

AU - Ortel, Thomas L.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Introduction Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. Objectives To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/Methods We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had 2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Results Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. Conclusion Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.

AB - Introduction Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. Objectives To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/Methods We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had 2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Results Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. Conclusion Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.

KW - deep-vein thrombosis

KW - gene expression profiling

KW - venous thrombosis

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