title: Elevated serum miR-93, miR-191, and miR-499 are noninvasive biomarkers for the presence and progression of traumatic brain injury.
abstract: The levels of miR-93, miR-191, and miR-499 have been reported to be up-regulated in the tissues of experimental traumatic brain injury (TBI) rat models. However, the clinical diagnostic and prognostic values of the serum signatures of these 3 miRNAs in TBI remain unclear. The purpose of this study was to determine the expression levels of these 3 microRNAs (miRNAs) in the sera of TBI patients and to evaluate their relationships with the severity and clinical outcome of TBI. The serum levels of these miRNAs were assessed in TBI patients (n = 76) and healthy controls (n = 38) by quantitative reverse-transcription PCR. The severities and clinical outcomes of the TBI patients were evaluated with the Glasgow coma scale and the Glasgow outcome scale. The serum miR-93, miR-191, and miR-499 levels were significantly increased in the TBI patients compared with the controls at all examined time points, and these levels were significantly higher in the patients with severe TBI than in those with moderate or mild TBI (p < 0.05). The serum miR-93, miR-191, and miR-499 levels were significantly higher in the patients with a poor outcome than in those with a good outcome (p < 0.05). The AUCs of miR-93, miR-191, and miR-499 for distinguishing the TBI patients from the healthy controls were 1.000 (p < 0.001), 0.727 (p < 0.001) and 0.801 (p < 0.001), respectively. Interestingly, the AUCs of miR-93, miR-191, and miR-499 for distinguishing the mild TBI patients from the healthy controls were 1.000 (p < 0.001), 0.742 (p < 0.001) and 0.819 (p < 0.001), respectively. Taken together, these results indicate that miR-93, miR-191, and miR-499 are potentially valuable indicators of the diagnosis, severity, and prognosis of TBI. Our study showed that the serum levels of miR-93, miR-191, and miR-499 are all increased in traumatic brain injury (TBI) patients. Their serum levels are associated with TBI severity and outcome, which suggest that these miRNAs play important roles in the pathogenesis and progression of TBI. We think these findings should provide a new strategy for the diagnostic, prognostic, and treatment of TBI.
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Jialu
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wan
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Chunni
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Junjun
authors.identifier: http://orcid.org/0000-0003-0507-1724
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001930:Brain Injuries / Q000097:blood* / Q000209:etiology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000502:physiology; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: C546177:MIRN191 microRNA, human; C548683:MIRN499 microRNA, human; C543350:MIRN93 microRNA, human; D035683:MicroRNAs
keywords: biomarkers; diagnosis; microRNA; qRT-PCR; traumatic brain injury