Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

Abstract

Background:Detection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility for use as TBI biomarkers in the acute phase of care. Methods:Publically-available microarray data generated from 31 postmortem human tissues was used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top five ranked miRNAs were then prospectively measured in serum samples collected from 10 TBI patients at hospital admission, as well as from 10 controls. Results:The top five miRNAs identified in our analysis (miR-137, miR-219a-5p, miR-128-3p, miR-124-3p, and miR-138-5p) exhibited 31 to 74-fold higher expression in brain relative to other tissues. Furthermore, their levels were elevated in serum from TBI patients compared to controls, and were collectively able to discriminate between groups with 90% sensitivity and 80% specificity. Subsequent informatic pathway analysis revealed that their target transcripts were significantly enriched for components of signaling pathways which are active in peripheral organs such as the heart. Conclusions:The five candidate miRNAs identified in this study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury. Introduction:Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States each year, and generates an estimated economic burden of $76.5 billion annually in total lifetime direct medical costs and productivity losses [1]. Quick recognition of TBI during triage avoids clinical delay and ensures patients are referred to an PREPRINT PREPRINT Brain Brain Brain Brain Brain Brain Brain Brain Brain Spinal cord Adipocyte Adipocyte