Abstract 17606: Unbiased Whole Blood RNA Profiling in Patients With Acute Coronary Syndrome and at Follow-Up
Introduction: Stabilized whole blood RNA samples are collected in clinical trials in acute coronary syndromes (ACS), using convenient tubes that are easily transported and stored. To date however, gene signatures, potential biomarkers for treatment effect or outcome, have not been comprehensively studied in unselected ACS patients. We aimed at establishing an unbiased whole blood gene expression profile of ACS patients and investigated to what extent it clusters with known clinical variables in the acute phase and at follow-up.
Methods: Peripheral blood RNA was profiled on the Affymetrix GeneChip® HTA 2.0 micro-array in patients with ACS on admission and at day 30 (n=65, 34 NSTEMI and 31 STEMI) and compared to stable CAD (n=22). An unbiased RNA signature was determined by differential expression between ACS and CAD (FDR p<0.001, fold change 2). At 1-year follow-up, 10 patients had experienced a new cardiovascular event, and 11 patients had developed ischemic cardiomyopathy.
Results: We established a gene signature consisting of 65 transcripts, of which 23 non-coding. The top transcripts include CLEC4D, MMP9, CLEC4E, LIPN, FKBP5, VNN1, IL1R2 and IRAK3, and are mainly involved in inflammatory signaling. This signature identified three separate gene expression clusters. Cluster 1 consisted significantly more of STEMI patients compared to cluster 2, that mainly identified NSTEMI patients (p=0.0001), without difference in peak troponin or CRP between these two clusters. Cluster 3 mainly identified stable CAD patients. In cluster 1, 27% of patients developed ischemic cardiomyopathy, compared to 17% in cluster 2 (p=N.S.). The signature did not discriminate between patients with vs. without new cardiovascular event. The individual genes contributing to the signature are highly correlated with infarct size (e.g. ρ = 0.57, p<0.001 for IL1R2) and the expression of selected transcripts in the acute phase significantly correlated with their residual expression at 30 days (e.g. R2=0.34, p<0.001 for LIPN).
Conclusion: Using this approach, an unbiased RNA signature in the acute phase of an ACS predominantly identifies patients with larger infarct size reflecting the type of ACS presentation, and correlates with residual expression levels at 30 days.
Author Disclosures: M. Vanhaverbeke: None. D. Veltman: None. T. Petit: None. S. Trenson: None. A. Wibowo: None. H. Gillijns: None. J. Bartunek: None. H.J. Huber: None. S. Janssens: None. P. Sinnaeve: None.
- © 2016 by American Heart Association, Inc.