MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury
MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury
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DOI：
10.1089/neu.2016.4857
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发表时间：
2017-06-01
影响因子：
4.2
通讯作者：
Belli, Antonio
中科院分区：
文献类型：
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作者：
Di Pietro, Valentina;Ragusa, Marco;Belli, Antonio
创伤性脑损伤（TBI）是西方国家45岁以下人群死亡和残疾的主要原因。尽管进行了许多研究，但尚未发现可靠的生物标志物来评估TBI的严重程度并预测康复。MicroRNA（miRNA）谱已被广泛用于鉴定生物标志物和治疗靶点。通过使用TaqMan Array Human MicroRNA A+B Cards，分析了5名轻度TBI（mTBI）伴颅外损伤（EC）患者、5名重度TBI（sTBI）伴EC患者和5名健康志愿者（HV）在损伤后1天和15天的血清中754种miRNA的表达。目的是找到能够区分mTBI和sTBI的候选生物标志物。在此之后，有可能通过在以下时间点使用单一TaqMan测定法在120名患者的扩大验证队列中选择10种miRNA用于进一步研究：T0-1 h、T4-12 h、T48-72 h和损伤后15天。分析揭示了两种miRNA（miR-425- 5 p和miR-502）在早期时间点在mTBI中显著下调（p < 0.05）并且是诊断mTBI的理想候选者，以及两种miRNA（miR-21和miR-335）显著上调（p < 0.01）并且是诊断sTBI的有效生物标志物。此外，miR-425- 5 p是T0-1 h和T4-12 h 6个月结局的强预测因子，而miR-21可预测T4-12 h的结局。所选miRNA组显示出作为区分mTBI与sTBI的生物标志物的前景。此外，选择的miRNAs代表了新的潜在治疗靶点。
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.