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.

Evaluation of serum miR-191-5p, miR-24-3p, miR-128-3p, and miR-376c-3 in multiple sclerosis patients

“…24 In the same publication, it was hypothesized that this increase could be due to active or passive miRNA release by injured brain tissue. 24 In the same publication, it was hypothesized that this increase could be due to active or passive miRNA release by injured brain tissue.…”

“…Moreover, increased levels of miR-191 have been reported in serum of patients with traumatic brain injury. 24 In the same publication, it was hypothesized that this increase could be due to active or passive miRNA release by injured brain tissue. Therefore, increased levels of miR-191 in blood of patients with MS may reflect release of the miRNAs due to apoptosis of neuronal as well as immune cells.…”

MicroRNA‑191‑5p exerts a tumor suppressive role in renal cell carcinoma

“…Several studies also reported that miR-191-5p may be of value as a prognostic and predictive biomarker in certain tumors, including breast cancer (44), osteosarcoma (45), and head and neck squamous cell carcinoma (46). Furthermore, miR-191-5p was suggested to be a potentially non-neoplastic biomarker to diagnose traumatic brain injury and predict the patient prognosis (47).…”

Blood biomarkers for brain injury: What are we measuring?

“…In the same study, miR-92a and miR-16 were able to specifically identify patients with mTBI from healthy controls with AUC values of 0.78 and 0.82, respectively (Redell et al, 2010). In addition, miR-93, miR-191, and miR-499 successfully distinguished mTBI patients from healthy controls with AUC values of 1.00, 0.74, and 0.82, respectively (Yang et al, 2016). Taken together, while the biological significance of miRNAs warrants further investigation, data obtained from the studies above suggest that serum miRNA levels may have diagnostic value in TBI.…”