title: Gene expression signature in peripheral blood detects thoracic aortic aneurysm.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Applied Biosystems, Foster City, California, United States of America.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Wang
authors.forename: Catalin C
authors.initials: CC
authors.lastname: Barbacioru
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Sriram
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Olga
authors.initials: O
authors.lastname: Iakoubova
authors.forename: Maryann
authors.initials: M
authors.lastname: Tranquilli
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Albornoz
authors.forename: Julie
authors.initials: J
authors.lastname: Blake
authors.forename: Necip N
authors.initials: NN
authors.lastname: Mehmet
authors.forename: Dewi
authors.initials: D
authors.lastname: Ngadimo
authors.forename: Karen
authors.initials: K
authors.lastname: Poulter
authors.forename: Frances
authors.initials: F
authors.lastname: Chan
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Samaha
authors.forename: John A
authors.initials: JA
authors.lastname: Elefteriades
mesh_terms: D017545:Aortic Aneurysm, Thoracic / Q000097:blood* / Q000175:diagnosis* / Q000601:surgery; D016022:Case-Control Studies; D016000:Cluster Analysis; D005189:False Positive Reactions; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic