Utility of Gene Expression Profiling Test Score Stability To Predict Future Clinical Events in Heart Transplant Recipients

Abstract

Purpose Gene-expression profiling (GEP) test scores have primarily been used to identify heart transplant recipients at low risk of rejection at the time of surveillance testing. We hypothesized that the stability of two or more intra-patient GEP test scores may also predict a lower risk of future allograft dysfunction or death. Methods and Materials Patients from the IMAGE study population with at least two surveillance GEP test scores were selected for this cohort study. GEP tests were performed at 3, 4, or 6 month intervals. Intra-patient GEP score stability was defined as the standard deviation of an individual’s cumulative test scores. GEP score (range 0-39), GEP score ≥34, and GEP score stability were studied in multivariate Cox regression models to predict future clinical events. Results In the cohort of 369 patients, race, age at transplantation, and time post-transplantation were significantly associated with future events. In the multivariate models, the GEP score stability gave a significant incremental accuracy in predicting future clinical events (p-value Figure 1 , where the upward shift of stability in event patients can be seen. The hazard ratio for a 1 unit increase in GEP score stability was 1.76 (1.4-2.3, 95% CI).[ figure1 ] Conclusions The stability of intra-individual GEP scores over time may enable personalized prediction of future risk of allograft dysfunction or death and may provide prognostic information beyond that rendered from individual GEP test scores. (ClinicalTrials.gov NCT00351559).