Document Detail


Detection of venous thromboembolism by proteomic serum biomarkers.
MedLine Citation:
PMID:  17579716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Available blood assays for venous thromboembolism (VTE) suffer from diminished specificity. Compared with single marker tests, such as D-dimer, a multi-marker strategy may improve diagnostic ability. We used direct mass spectrometry (MS) analysis of serum from patients with VTE to determine whether protein expression profiles would predict diagnosis.
METHODS AND RESULTS: We developed a direct MS and computational approach to the proteomic analysis of serum. Using this new method, we analyzed serum from inpatients undergoing radiographic evaluation for VTE. In a balanced cohort of 76 patients, a neural network-based prediction model was built using a training subset of the cohort to first identify proteomic patterns of VTE. The proteomic patterns were then validated in a separate group of patients within the cohort. The model yielded a sensitivity of 68% and specificity of 89%, which exceeded the specificity of D-dimer assay tested by latex agglutination, ELISA, and immunoturbimetric methods (sensitivity/specificity of 63.2%/60.5%, 97.4%/21.1%, 97.4%/15.8%, respectively). We validated differences in protein expression between patients with and without VTE using more traditional gel-based analysis of the same serum samples.
CONCLUSION: Protein expression analysis of serum using direct MS demonstrates potential diagnostic utility for VTE. This pilot study is the first such direct MS study to be applied to a cardiovascular disease. Differences in protein expression were identified and subsequently validated in a separate group of patients. The findings in this initial cohort can be evaluated in other independent cohorts, including patients with inflammatory conditions and chronic (but not acute) VTE, for the diagnosis of VTE.
Authors:
Santhi K Ganesh; Yugal Sharma; Judith Dayhoff; Henry M Fales; Jennifer Van Eyk; Thomas S Kickler; Eric M Billings; Elizabeth G Nabel
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-20
Journal Detail:
Title:  PloS one     Volume:  2     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2007  
Date Detail:
Created Date:  2007-06-20     Completed Date:  2010-04-29     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e544     Citation Subset:  IM    
Affiliation:
National Heart, Lung and Blood Institute, Bethesda, Maryland, United States of America; National Human Genome Research Institute, Bethesda, Maryland, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Cohort Studies
Diabetes Complications / blood
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Female
Fibrin Fibrinogen Degradation Products / metabolism
Heart Diseases / blood,  complications
Humans
Kidney Diseases / blood,  complications
Lung Diseases / blood,  complications
Male
Middle Aged
Neoplasms / blood,  complications
Neural Networks (Computer)
Pilot Projects
Prognosis
Proteomics*
Sensitivity and Specificity
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tumor Markers, Biological / blood*
Venous Thromboembolism / blood*,  diagnosis*
Grant Support
ID/Acronym/Agency:
N0-HV-28120/HV/NHLBI NIH HHS; N01 HV028180/HV/NHLBI NIH HHS; RC1 HL100021-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibrin Fibrinogen Degradation Products; 0/Tumor Markers, Biological; 0/fibrin fragment D
Comments/Corrections

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