Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury.
Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury.
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血浆miR - 9 - 3p和miR - 136 - 3p作为实验性及人类轻度创伤性脑损伤潜在的新型诊断生物标志物
DOI：
10.3390/ijms22041563
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发表时间：
2021-02-04
影响因子：
5.6
通讯作者：
Pitkänen A
中科院分区：
文献类型：
--
作者：
Das Gupta S;Ciszek R;Heiskanen M;Lapinlampi N;Kukkonen J;Leinonen V;Puhakka N;Pitkänen A
对于难以诊断的轻度创伤性脑损伤（mTBI），无创且价格合理的循环生物标志物是一项尚未满足的医疗需求。尽管据报道创伤性脑损伤（TBI）后血液微小核糖核酸（miRNA）水平会发生改变，但其对mTBI的诊断潜力仍不确定。我们假设急性改变的血浆miRNAs可在侧方液压冲击伤（FPI）模型和临床mTBI中作为诊断生物标志物。我们在创伤性脑损伤后2天对成年雄性斯普拉格 - 道利大鼠（n = 31）进行了血浆小核糖核酸测序，随后对选定的候选物进行了基于聚合酶链反应（PCR）的验证。在侧方FPI后2天，miR - 9a - 3p、miR - 136 - 3p和miR - 434 - 3p被确定为最有希望的候选物。数字微滴聚合酶链反应（ddPCR）显示miR - 9a - 3p、miR - 136 - 3p和miR - 434 - 3p水平分别升高4.2倍、2.8倍和4.6倍（所有均p < 0.01），能够以100%的敏感性和特异性区分mTBI大鼠和未受伤大鼠。ddPCR进一步确定了一部分mTBI患者，其在伤后<2天血浆miR - 9 - 3p（n = 7/15）和miR - 136 - 3p（n = 5/15）水平高于对照均值一个标准差。在重度创伤性脑损伤（sTBI）患者中，血浆miR - 9 - 3p水平分别是mTBI组和对照组的6.5倍和9.2倍。因此，血浆miR - 9 - 3p和miR - 136 - 3p被确定为mTBI有希望的生物标志物候选物，需要在更大的患者群体中进一步评估。
Noninvasive, affordable circulating biomarkers for difficult-to-diagnose mild traumatic brain injury (mTBI) are an unmet medical need. Although blood microRNA (miRNA) levels are reportedly altered after traumatic brain injury (TBI), their diagnostic potential for mTBI remains inconclusive. We hypothesized that acutely altered plasma miRNAs could serve as diagnostic biomarkers both in the lateral fluid percussion injury (FPI) model and clinical mTBI. We performed plasma small RNA-sequencing from adult male Sprague–Dawley rats (n = 31) at 2 days post-TBI, followed by polymerase chain reaction (PCR)-based validation of selected candidates. miR-9a-3p, miR-136-3p, and miR-434-3p were identified as the most promising candidates at 2 days after lateral FPI. Digital droplet PCR (ddPCR) revealed 4.2-, 2.8-, and 4.6-fold elevations in miR-9a-3p, miR-136-3p, and miR-434-3p levels (p < 0.01 for all), respectively, distinguishing rats with mTBI from naïve rats with 100% sensitivity and specificity. DdPCR further identified a subpopulation of mTBI patients with plasma miR-9-3p (n = 7/15) and miR-136-3p (n = 5/15) levels higher than one standard deviation above the control mean at <2 days postinjury. In sTBI patients, plasma miR-9-3p levels were 6.5- and 9.2-fold in comparison to the mTBI and control groups, respectively. Thus, plasma miR-9-3p and miR-136-3p were identified as promising biomarker candidates for mTBI requiring further evaluation in a larger patient population.
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