Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF/OIF Veterans

摘要

This study was designed to identify clinically accessible molecular biomarkers of mild traumatic brain injury (mTBI) that could be used to help identify returning Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) Veterans who are suffering from the effects of mTBI. While analyzing the expression profile of small non-coding RNAs in peripheral blood mononuclear cells (PBMCs) from an OEF/OIF veteran study cohort using a high throughput array chip platform, we identified 18 candidate small non-coding RNA biomarkers that are differentially regulated in PBMCs of mTBI compared to non-TBI control cases. Independent quantitative real-time polymerase chain reaction assays confirmed that 13 of these candidate small RNA biomarker species are, indeed, significantly down-regulated in PBMCs of mTBI compared to non-TBI control veteran cases. Based on unsupervised clustering analysis, we identified a 3-biomarker panel which was most able to distinguish mTBI from non-TBI control veteran cases with high accuracy, selectivity and specificity. The majority of mTBI cases in our biomarker study were co-morbid with Post-Traumatic Stress Disorder (PTSD), and thus our non-TBI control cases were selected to match PTSD diagnoses. Therefore, our identified panel of 3 small RNA biomarkers likely represents a biological index selective for mTBI. Outcomes from our studies suggest that additional applications of the clinically accessible small non-coding RNA biomarkers to current diagnostic criteria may lead to improved mTBI detection and more sensitive outcome measures for clinical trials. Future studies exploring the physiological relevance of mTBI biomarkers will also provide a better understanding of the biological mechanisms underlying mTBI and insights into novel therapeutic targets for mTBI.