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Prediction of ischemic events on the basis of transcriptomic and genomic profiling in patients undergoing carotid endarterectomy - PubMed

  • ️Sun Jan 01 2012

Prediction of ischemic events on the basis of transcriptomic and genomic profiling in patients undergoing carotid endarterectomy

Lasse Folkersen et al. Mol Med. 2012.

Abstract

Classic risk factors, including age, smoking, serum cholesterol, diabetes and blood pressure, constitute the basis of present risk prediction models but fail to identify all individuals at risk. The objective of this study was to investigate if genomic and transcriptional patterns improve prediction of ischemic events in patients with established carotid artery disease. Genotype and gene expression profiles were obtained from carotid plaque tissue (n = 126) and peripheral blood mononuclear cells (n = 97) of patients undergoing carotid endarterectomy. Patients were followed for an average of 44 months, and 25 ischemic events occurred (18 ischemic strokes and 7 myocardial infarctions). Blinded leave-one-out cross-validation on Cox regression coefficients was used to assign gene expression-based risk scores to each patient. When compared with classic risk factors, addition of carotid plaque gene expression-based risk score improved the prediction of future ischemic events from an area under the curve (AUC) of 0.66 to an AUC of 0.79. The inclusion of gene expression risk score from peripheral blood mononuclear cells or from 25 established myocardial infarction risk single nucleotide polymorphisms only exhibited marginal effects on the prediction of ischemic events. Prediction of ischemic events is improved by inclusion of gene expression profiling from carotid endarterectomy tissue compared with prediction on the basis of classic risk markers alone in patients with atherosclerosis. The method may be developed to identify subjects at very high risk of ischemic events.

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Figures

Figure 1
Figure 1

Flow diagram of cross-validation scheme. R-code for this scheme can be found as Supplementary Table 4.

Figure 2
Figure 2

Kaplan-Meier plot of ischemic events stratified by gene expression. The plot shows the fraction of event-free survival as a function of months after operation. Each line represents half of the 126 plaque samples: the gray line denotes the group with expression risk scores below the median, and the black line denotes the group with expression risk scores above the median.

Figure 3
Figure 3

Receiver operated characteristic curves for different risk factors at 300 d. Top plots show data from the plaque data set. Bottom plots show data from the PBMC data set. Plots are calculated only from gene expression profiles (left), only from the established risk factors: age, gender, LDL and smoking (middle), or from both gene expression profile and the four established risk factors (left). The straight diagonal line illustrates prediction by pure chance (AUC 0.5), and the curved line describes the prediction possible with the given predictive variables. A theoretical curve along the top left corner would indicate perfect prediction (AUC 1).

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