Abstract 13338: A Molecular Signature with the Potential for Identifying Impending Acute Myocardial Infarction
The inability to temporally and accurately predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Prior work investigating the potential of circulating endothelial cells (CECs) as a biomarker for AMI has focused mainly on increased enumeration in AMI. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for AMI present in whole blood of patients that was determined using microarray analysis of enriched CECs. Using CELLSEARCH® technology we first separated and enriched CECs from the peripheral blood of patients with AMI (n=53) or from healthy controls (n=53). Total RNA was analyzed using the Affymetrix Human U133 Plus 2.0 Microarray for the expression of over 47,000 transcripts. The expression profiles were examined to determine which genes were selectively up-regulated in AMI compared to controls. We nominated 19 candidate genes from the microarray analysis that demonstrated the ability to discriminate between AMI and controls. To determine if these discriminatory profiles can be detected in samples processed without CEC enrichment, we performed qRT-PCR on the candidate genes using the whole blood of patients with AMI (n=46) and healthy controls (n=30). Heparin-binding EGF-like growth factor (HBEGF) showed the highest discriminatory performance between MI and controls (AUC 0.961, 0.887-0.992, p< 0.0001) in the whole blood analysis. This was followed by NR4A2 (AUC 0.886), NR4A3 (AUC 0.863), EFEMP1 (AUC 0.888), NFKBIA (AUC 0.814) and NLRP3 (AUC 0.811) (p<0.0001 for all). A linear combination of the weighted scores for these 6 genes discriminated AMI from controls with an AUC of 0.97 (p<0.0001). Further study will determine if this proposed six gene molecular signature will lead to the first gene-based, point-of-care testing for the prediction of AMI in an at-risk population.
Author Disclosures: E.D. Muse: None. H. Wang: None. P. Barrett: None. F. Parviz: None. M.A. Novotny: None. R.S. Lasken: None. T.A. Jatkoe: None. M.C. Connelly: None. K.M. Schilling: None. C. Rao: None. A. Torkamani: None. E.J. Topol: Research Grant; Modest; Johnson & Johnson.
- © 2014 by American Heart Association, Inc.