Date of Award
Open Access Thesis
Medical Doctor (MD)
John A. Elefteriades
Thoracic aortic aneurysms (TAAs) are clinically-silent diseases that predispose individuals to life-threatening aortic dissection or rupture. If detected early, TAAs can be safely treated with elective surgery. Therefore, there is a great clinical need in screening for TAAs. However, no reliable screening programs exist, and radiographic imaging is too costly and harmful for screening entire at-risk populations. We hypothesize that a novel diagnostic blood test based on the gene-expression profiles of a previously-identified panel of 41 genes (a RNA signature) is greater than 70% sensitive in detecting TAAs. Using RNA extracted from peripheral blood cells of 40 individuals (24 TAA patients and 16 spousal controls), we performed real-time PCR using customized TaqMan Array Cards to analyze the relative expression levels of this panel of genes. A 10-fold cross-validation study based on these expression levels was used to predict whether each sample belonged to a TAA patient or a spousal control. When compared with each sample's true clinical status, this RNA signature-based prediction model was 83% accurate, with a sensitivity of 88% and a specificity of 75%. Furthermore, the expression levels of the individual genes were largely consistent with their expression levels from a previous study of this RNA signature (r2 = 0.75 for TAA patient samples, and r2 = 0.73 for spousal control samples), supporting the reproducibility of this test. Altogether, these findings demonstrate that gene-expression profiling is an accurate, sensitive, and reliable method for detecting TAAs. If utilized as a clinical screening test, this RNA signature has the potential to detect silent TAAs, leading to earlier diagnosis and reduced mortality of this dangerous condition.
Sang, Adam, "Gene Expression Signature As A Diagnostic Test For Thoracic Aortic Aneurysms: A Validation Study" (2013). Yale Medicine Thesis Digital Library. 1840.