Serum miRNA-based signature to identify radiation exposure and dose in humans

Previously, we used mouse and non-human primate models to show that serum miRNAs may predict the biological impact of lethal and sublethal radiation doses. We hypothesized that these results can be replicated in humans treated with total body irradiation (TBI), and that miRNAs may be used as clinically feasible biodosimeters. To test this hypothesis, serial serum samples were obtained from 25 patients who underwent allogeneic stem-cell transplantation and profiled for miRNA expression using next-generation sequencing. Differential expression results were largely consistent with previous studies and allowed us to select miRNAs, including miR-150-5p, miR-126-5p, miR-375, miR-215-5p, miR-144-5p, miR-122-5p, miR-320d and miR-10b-5p to build classifiers using qPCR-based quantification. We therefore conclude that serum miRNAs reflect radiation exposure and dose for humans undergoing TBI and may be used as functional biodosimeters for precise identification of people exposed to clinically significant radiation doses. Overall design: Serial serum and serum-isolated exosome miRNA profiles of 25 patients (children and adults) subjected to total body irradiation (total 71 samples)