Bioinformatic Identification of Candidate miRNA Biomarkers for Traumatic Brain Injury

Abstract

The identification of peripheral blood biomarkers which are associated with traumatic brain injury (TBI) could lead to the development of molecular diagnostics which could be used to aid acute detection in scenarios where neuroimaging in unavailable, or to remotely track injury progression and recovery. It is becoming increasingly evident that brain tissue exhibits patterns of micro‐RNA (miRNA) expression which are distinct from those of other tissues. During TBI, the blood brain barrier becomes disrupted and molecules from damaged neural tissues are released into peripheral circulation. Thus, the detection of brain specific miRNAs in peripheral blood could serve as a surrogate marker of TBI. In this investigation, we aimed to systematically identify brain‐enriched miRNAs, and then test their potential utility for use as TBI biomarkers. First, we obtained publically‐available expression data for over 1,300 miRNAs generated from 31 different human post‐mortem tissues. Tissue specificity index (Tau) was calculated for each miRNA, and they were subsequently ranked in terms of their degree of brain‐specific expression. The abundances of the top five ranked miRNAs were then measured in serum samples collected from 10 TBI patients and 10 healthy controls using qPCR, and evaluated for their ability to discriminate between groups using k‐nearest neighbors (k‐NN). The top five miRNAs identified in our tissue specificity analysis consisted of miR‐137, miR‐219a‐5p, miR‐128‐3p, miR‐124‐3p, and miR‐138‐5p, which exhibited from 31 to 74‐fold higher expression levels in brain relative to other tissues. Three out of the five candidate miRNAs exhibited significantly higher abundance in serum samples from TBI patients relative to control patients in qPCR analysis, and their coordinate expression levels were able to discriminate between groups with 90% sensitivity and 80% specificity. The five candidate miRNAs identified in our analysis have potential utility for use as TBI biomarkers, and such a possibility warrants further investigation.Support or Funding InformationWork was supported by Case Western Reserve University FPB School of Nursing start‐up funds issued to Grant C. O'Connell.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.