616: Comparison of circulating extracellular vesicle versus plasma proteins for prediction of spontaneous preterm birth

Abstract

Extracellular vesicles (EVs) provide a novel and increasingly useful source of proteomic information separate from protein analysis in plasma alone. We hypothesize that EV protein profiling and analysis will provide a unique group of protein biomarkers for spontaneous preterm births compared to direct analysis of free plasma proteins. Twenty-five sPTB and 50 term EDTA plasma specimens were obtained at a median of 25 weeks gestation and matched by maternal age, race and gestational age at sampling. Vesicles were isolated from one aliquot via size exclusion chromatography (SEC) and the other was left as plasma (PPS). Both samples were analyzed by multiple reaction monitoring mass spectrometry for a targeted set of proteins. Data from the SEC and PPS samples was analyzed with a bootstrap receiver-operator curve (ROC) analysis that was performed with label permutation for a false discovery rate <20% for the identification of sPTB. The permutation test of Venkatraman was used to compare the significance of the area under the curve (AUC) in the SEC and PPS fractions for each of the top paired candidate markers. Of the 132 proteins evaluated, the median relative concentrations in the plasma versus EV samples for each protein are presented in the figure which illustrate little similarity between the fractions. The top ten bootstrapped AUCs, with regard to the prediction of sPTB, are presented in Table 1. The AUCs among the SEC were significantly higher than the corresponding PPS with no overlap in the top performing proteins between the two fractions. Among the top single marker predictors of sPTB from both EV and plasma proteins, the EV protein markers tended to display significantly better ROC characteristics. Circulating EV associated proteins represent a source of biomarker information that is distinct from proteins derived directly from the plasma.View Large Image Figure ViewerDownload Hi-res image Download (PPT)