Personalized Medicine in Veterans with Traumatic Brain Injuries

Abstract

Abstract : The study was designed to identify clinically accessible molecular biomarkers of traumatic brain injury (TBI) prior to definitive clinical diagnosis using high throughput microRNA technology. Specifically, these studies were meant to identify, characterize, and validate microRNA biomarker species whose content in peripheral blood mononuclear cells (PBMC) could help to distinguish TBI cases from the Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) veteran population. During the past years, we conducted a Biomarker Discovery study using a high-throughput Array chip platform and identified 18 candidate TBI small RNA biomarkers. Using independent Q-PCR assays, we confirmed that 13 of these candidate small RNA biomarker species are, indeed, significantly down-regulated in PBMC of TBI compared to non-TBI control veteran cases. Additionally, we used unsupervised clustering analysis and demonstrated that the differential regulation of these small RNA biomarkers in clinically accessible blood cells is capable of distinguishing between TBI and non-TBI OEF/OIF veteran cases. Lastly, we identified a 3-biomarker panel capable of distinguishing TBI from non-TBI control veteran cases with 89% accuracy 82% selectivity and 78% specificity. The majority of TBI cases in our biomarker study were co-morbid with PTSD, and our non-TBI control cases were selected to match for PTSD diagnosis. Thus, our identified panel of 13 small RNA biomarkers likely represents biological indices selective for TBI. During the past year, we recruited 13 new cases (6 TBI and 7 non-TBI cases). Together with the cases recruited in previous years, we currently have a total of 83 cases, comprised of 17 TBI and 66 non-TBI control cases, which are available for Biomarker Validation studies.