Gene expression signature in peripheral blood detects thoracic aortic aneurysm.

<h4>Background</h4>Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yulei Wang, Catalin C Barbacioru, Dov Shiffman, Sriram Balasubramanian, Olga Iakoubova, Maryann Tranquilli, Gonzalo Albornoz, Julie Blake, Necip N Mehmet, Dewi Ngadimo, Karen Poulter, Frances Chan, Raymond R Samaha, John A Elefteriades
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/581d10329fa14eddad3be7a8537cb8e6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:581d10329fa14eddad3be7a8537cb8e6
record_format	dspace
spelling	oai:doaj.org-article:581d10329fa14eddad3be7a8537cb8e62021-11-25T06:10:40ZGene expression signature in peripheral blood detects thoracic aortic aneurysm.1932-620310.1371/journal.pone.0001050https://doaj.org/article/581d10329fa14eddad3be7a8537cb8e62007-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0001050https://doaj.org/toc/1932-6203<h4>Background</h4>Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA.<h4>Methods and findings</h4>Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set.<h4>Conclusions</h4>This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA.Yulei WangCatalin C BarbacioruDov ShiffmanSriram BalasubramanianOlga IakoubovaMaryann TranquilliGonzalo AlbornozJulie BlakeNecip N MehmetDewi NgadimoKaren PoulterFrances ChanRaymond R SamahaJohn A ElefteriadesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 2, Iss 10, p e1050 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yulei Wang Catalin C Barbacioru Dov Shiffman Sriram Balasubramanian Olga Iakoubova Maryann Tranquilli Gonzalo Albornoz Julie Blake Necip N Mehmet Dewi Ngadimo Karen Poulter Frances Chan Raymond R Samaha John A Elefteriades Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
description	<h4>Background</h4>Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA.<h4>Methods and findings</h4>Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set.<h4>Conclusions</h4>This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA.
format	article
author	Yulei Wang Catalin C Barbacioru Dov Shiffman Sriram Balasubramanian Olga Iakoubova Maryann Tranquilli Gonzalo Albornoz Julie Blake Necip N Mehmet Dewi Ngadimo Karen Poulter Frances Chan Raymond R Samaha John A Elefteriades
author_facet	Yulei Wang Catalin C Barbacioru Dov Shiffman Sriram Balasubramanian Olga Iakoubova Maryann Tranquilli Gonzalo Albornoz Julie Blake Necip N Mehmet Dewi Ngadimo Karen Poulter Frances Chan Raymond R Samaha John A Elefteriades
author_sort	Yulei Wang
title	Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
title_short	Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
title_full	Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
title_fullStr	Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
title_full_unstemmed	Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
title_sort	gene expression signature in peripheral blood detects thoracic aortic aneurysm.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/581d10329fa14eddad3be7a8537cb8e6
work_keys_str_mv	AT yuleiwang geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT catalincbarbacioru geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT dovshiffman geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT srirambalasubramanian geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT olgaiakoubova geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT maryanntranquilli geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT gonzaloalbornoz geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT julieblake geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT necipnmehmet geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT dewingadimo geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT karenpoulter geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT franceschan geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT raymondrsamaha geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm AT johnaelefteriades geneexpressionsignatureinperipheralblooddetectsthoracicaorticaneurysm
_version_	1718414102086287360

Gene expression signature in peripheral blood detects thoracic aortic aneurysm.

Ejemplares similares