title: MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) is the leading cause of death and disability in people younger than 45 in Western countries. Despite many studies, no reliable biomarkers have been found to assess TBI severity and predict recovery. MicroRNA (miRNA) profiling has become widely used to identify biomarkers and therapeutic targets. Through use of the TaqMan Array Human MicroRNA A+B Cards, the expression of 754 miRNAs was analyzed in serum of five mild TBI (mTBI) patients with extra-cranial injury (EC), five severe TBI (sTBI) patients with EC, and five healthy volunteers (HV) at 1 day and 15 days post-injury. The aim was to find candidate biomarkers able to discriminate between mTBI and sTBI. Following this, it was possible to select 10 miRNAs for further study in an enlarged validation cohort of 120 patients by using single TaqMan assays at the following time-points: T0-1 h, T4-12 h, T48-72 h, and 15 days from the injury. Analysis revealed two miRNAs (miR-425-5p and miR-502) that were significantly downregulated (p < 0.05) in mTBI at early time-points and are ideal candidates for diagnosis of mTBI, and two miRNAs (miR-21 and miR-335) that were significantly upregulated (p < 0.01) and are valid biomarkers for the diagnosis of sTBI. In addition, miR-425-5p was a strong predictor of 6-month outcome at T0-1 h and T4-12 h, while miR-21 was predictive of the outcome at T4-12 h. The panel of selected miRNAs shows promise as biomarkers to discriminate mTBI from sTBI. In addition, the selected miRNAs represent new potential therapeutic targets.
authors.affiliation: 1 Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham , Birmingham, United Kingdom .|2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Pietro
authors.affiliation: 3 Department of Biomedical Sciences and Biotechnology, University of Catania , Catania, Italy .
authors.forename: Marco
authors.initials: M
authors.lastname: Ragusa
authors.affiliation: 2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: David
authors.initials: D
authors.lastname: Davies
authors.affiliation: 2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: Zhangjie
authors.initials: Z
authors.lastname: Su
authors.affiliation: 1 Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham , Birmingham, United Kingdom .|2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: Jon
authors.initials: J
authors.lastname: Hazeldine
authors.affiliation: 4 Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome , Rome, Italy .
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lazzarino
authors.affiliation: 1 Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham , Birmingham, United Kingdom .|2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Hill
authors.affiliation: 2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .|5 West Midlands Air Ambulance Trust , West Midlands, United Kingdom .
authors.forename: Nicholas
authors.initials: N
authors.lastname: Crombie
authors.affiliation: 6 Academic Department of Military Surgery and Trauma, Royal Center for Defense Medicine, Institute of Research and Development , Birmingham, United Kingdom .
authors.forename: Mark
authors.initials: M
authors.lastname: Foster
authors.affiliation: 3 Department of Biomedical Sciences and Biotechnology, University of Catania , Catania, Italy .
authors.forename: Michele
authors.initials: M
authors.lastname: Purrello
authors.affiliation: 1 Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham , Birmingham, United Kingdom .|2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: Ann
authors.initials: A
authors.lastname: Logan
authors.affiliation: 1 Neurotrauma and Ophthalmology Research Group, Institute of Inflammation and Aging, University of Birmingham , Birmingham, United Kingdom .|2 National Institute for Health Research Surgical Reconstruction and Microbiology Research Center , Queen Elizabeth Hospital, Birmingham, United Kingdom .
authors.forename: Antonio
authors.initials: A
authors.lastname: Belli
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001924:Brain Concussion / Q000097:blood / Q000175:diagnosis; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000175:diagnosis*; D003933:Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biomarkers; concussion; diagnosis; microRNAs; prognosis; traumatic brain injury