Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm

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 assays define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA. Keywords: Gene Expression Signature Whole Genome gene expression profiles from a total of 94 peripheral blood samples (collected from 58 individuals diagnosed with TAA and 36 normal controls) were analyzed in this study. Significance Analysis of Microarray (SAM) analysis identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, as well as 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 eplicated the microarray results and achieved 80% classification accuracy on the testing set.