创伤性脑损伤患者血清miR-422a水平变化的初步探讨

Preliminary study on altered levels of serum miR-422a in patients with traumatic brain injury

目的检测创伤性脑损伤(traumatic brain injury,TBI)患者血清miR-422a的表达水平,探讨其作为TBI诊断及预后判断指标的临床应用价值。方法采用TaqMan实时荧光定量聚合酶链反应(qRT-PCR)检测75例轻度创伤性脑损伤(mTBI)、75例重度创伤性脑损伤(sTBI)及75例健康人对照者血清miR-422a的表达水平,比较CT阳性和阴性患者血清miR-422a表达水平的差异;采用ROC曲线评估miR-422a对mTBI和sTBI的诊断效能,Spearman相关性分析评估miR-422a与TBI患者病情和预后的关系。结果与健康人对照组[(31.1×10^-5(18×10^-5,51.5×10^-5)]相比,mTBI[81.6×10^-5(51.2×10^-5, 131.1×10^-5)]和sTBI[132.5×10^-5(51.5×10^-5,240.5×10^-5)]患者血清miR-422a水平均明显升高(Z=-6.647,P<0.001;Z=-7.345,P<0.001),且sTBI患者血清miR-422a水平明显高于mTBI患者(Z=-2.573,P=0.01)。ROC曲线分析显示,miR-422a用于鉴别健康人对照组与TBI患者的曲线下面积(AUCROC)为0.831(95%CI:0.776~0.886,P<0.001);用于鉴别健康人对照组与mTBI患者的AUCROC为0.814(95%CI:0.744~0.885,P<0.001);用于鉴别健康人对照组与sTBI患者的AUCROC为0.847(95%CI:0.785~0.910,P<0.001)。TBI患者CT阳性组血清miR-422a水平明显高于CT阴性组(P=0.025)。此外,TBI患者预后较差组的miR-422a表达水平明显高于预后较好组(P=0.031)。相关性分析显示,TBI患者血清miR-422a的表达水平与GCS评分(r=-0.231,P=0.004)、GOS评分(r=-0.208,P=0.011)均呈负相关。结论 TBI患者血清miR-422a表达水平明显升高,且与病情和预后相关,是潜在的TBI辅助诊断指标。

Objective To detect the altered levels of miR-422 a in serum of traumatic brain injury(TBI) patients and explore its clinical value as diagnostic and prognostic indicator for TBI. Methods Serum miR-422 a levels were determined by TaqMan quantitative real-time polymerase chain reaction(qRT-PCR) in 75 mild traumatic brain injury(mTBI) patients, 75 severe traumatic brain injury(sTBI) patients and 75 healthy controls. The differences of serum miR-422 a levels were compared between the TBI patients with and without lesions on head CT. Receiver operating characteristic(ROC) curve analyses were used to evaluate the diagnostic efficacy of miR-422 a for mTBI and sTBI patients. Spearman correlation analysis was used to assess the relationship between the levels of miR-422 a and the severity and prognosis of TBI patients. Results Compared with healthy controls [(31.1×10-5(18×10-5, 51.5×10-5)], the serum miR-422 a level was significantly increased in both the patients of mTBI 81.6×10-5(51.2×10-5, 131.1×10-5)(Z=-6.647, P<0.001)]and sTBI [132.5×10-5(51.5×10-5, 240.5×10-5)(Z=-7.345, P<0.001)]. The serum miR-422 a level of sTBI patients was significantly higher than that of mTBI patients(Z=-2.573, P=0.01). The area under ROC curve(AUCROC) of miR-422 a for distinguishing healthy controls from TBI patients was 0.831(95%CI: 0.776 to 0.886, P<0.001). The AUCROC of miR-422 a for distinguishing healthy controls from mTBI patients was 0.814(95%CI: 0.744 to 0.885, P<0.001). The AUCROC of miR-422 a for distinguishing healthy controls from sTBI patients was 0.847(95%CI: 0.785 to 0.910, P<0.001). miR-422 a level of the TBI patients with lesions on head CT were significantly increased compared with that without lesions on head CT(P=0.025). In addition, the level of miR-422 a in TBI patients with unfavorable outcome was significantly higher than that in TBI patients with favorable outcome(P=0.031). Spearman correlations analysis showed that the level of the miR-422 a was significantly negatively correlated with GCS score(Glasgow coma scale)(r=-0.231, P=0.004) and GOS score(Glasgow outcome scale)(r=-0.208, P=0.011). Conclusion The level of serum miR-422 a in TBI patients was significantly increased and related to the condition and prognosis of TBI patients. Serum miR-422 a may be a potential biomarker for the assessment of diagnosis and prognosis of TBI patients.