脊柱骨折并发脊髓损伤患者血清miR-22-3p、miR-210表达水平及其对预后的预测价值

Expression levels of serum miR-22-3p and miR-210 in patients with spinal fractures complicated with spinal cord injury and their prognostic values

中文关键词:  脊柱骨折  脊髓损伤  微小RNA-22-3p  微小RNA-210  预后

英文关键词:Spinal fracture  Spinal cord injury  MicroRNA-22-3p  MicroRNA-210  Prognosis

中文摘要:

  【摘要】　目的：探讨脊柱骨折并发脊髓损伤患者血清miR-22-3p和miR-210的表达水平及其对预后的预测价值，分析影响患者预后的相关因素。方法：选取2023年3月~2024年6月华北医疗健康集团邢台总医院收治的106例脊柱骨折并发脊髓损伤患者作为脊髓损伤组，98例单纯脊柱骨折患者作为单纯骨折组。依据美国脊髓损伤协会（American Spinal Injury Association，ASIA）分级将脊髓损伤组患者分为不完全损伤组（ASIA分级B、C、D级，n=67例）和完全损伤组（ASIA分级A级，n=39例）；根据术后3个月ASIA分级较入院时的变化，将脊髓损伤组患者分为改善组（75例）和恶化组（31例）。另选取同期河北大学附属医院收治的72例脊柱骨折并发脊髓损伤患者作为外部验证组，其中改善组51例，恶化组21例。收集所有研究对象（脊髓损伤组、单纯骨折组、外部验证组）的年龄、性别、既往病史、致病原因、骨折部位，并收集脊髓损伤组患者的：是否为多节段脊髓损伤、椎管侵占率、脊髓损伤情况、受伤至手术时间、受伤至使用激素（甲泼尼龙）时间。所有患者手术前清晨采集空腹静脉血，采用逆转录实时定量聚合酶链式反应（real-time quantitative reverse transcription PCR，RT-qPCR）法检测血清miR-22-3p和miR-210水平，比较各组血清miRNA水平差异；采用Spearman相关性分析脊髓损伤组血清miR-22-3p、miR-210与脊髓损伤情况（完全/不完全损伤）的关系；Pearson相关性分析脊髓损伤组miR-22-3p和miR-210的关系；Logistic回归分析预后的影响因素，受试者工作特征（receiver operating characteristic，ROC）曲线评估血清miR-22-3p和miR-210对预后的预测效能，曲线下面积（area under the curve，AUC）比较采用DeLong检验。将基于训练组构建的预测模型在外部验证组中进行验证，评估其区分度。结果：脊髓损伤组、单纯骨折组、外部验证组三组患者的年龄、性别、既往病史、致病原因、骨折部位比较，均无统计学差异（P>0.05）。相比单纯骨折组，外部验证组和脊髓损伤组血清miR-22-3p水平显著性升高，miR-210水平显著性降低（P<0.05）；与不完全损伤组相比，完全损伤组血清miR-22-3p显著性升高（1.52±0.33 vs 1.19±0.25），miR-210显著性降低（0.61±0.14 vs 0.83±0.18）（P＜0.05）。Spearman相关性分析显示，脊髓损伤组血清miR-22-3p与脊髓损伤程度呈正相关（r=0.511，P＜0.001），miR-210与脊髓损伤程度呈负相关（r=-0.487，P＜0.05）；Pearson相关性分析显示，miR-22-3p和miR-210呈负相关（r=-0.460，P＜0.05）。恶化组椎管侵占率≥50%的比例（58.06% vs 34.67%）、受伤至使用激素类药物时间≥8h的比例（61.29% vs 38.67%）以及血清miR-22-3p水平（1.62±0.32 vs 1.18±0.26）均显著性高于改善组，血清miR-210水平显著低于改善组（0.58±0.12 vs 0.82±0.17）（P＜0.05）。多因素logistic回归分析显示，椎管侵占率≥50%、受伤至使用激素（甲泼尼龙）时间≥8h、miR-22-3p水平升高和miR-210水平升高是预后不良的影响因素（P＜0.05）。ROC分析显示，miR-22-3p和miR-210联合预测的AUC显著性高于miR-22-3p（Z=2.052，P=0.040）、miR-210（Z=1.994，P=0.046）单独预测。外部验证中，miR-22-3p和miR-210联合预测的AUC为0.919，敏感度为76.19%，特异度为96.08%。结论：脊柱骨折并发脊髓损伤患者血清miR-210水平显著性降低，血清miR-22-3p水平显著性升高，与脊髓损伤程度相关。miR-22-3p和miR-210联合检测对患者结局具有较高的预测价值。

英文摘要:

  【Abstract】 Objectives: To investigate the serum expression levels of miR-22-3p and miR-210 in patients with spinal fractures complicated with spinal cord injury, as well as their prognostic values, and to analyze the factors influencing patient prognosis. Methods: A retrospective cohort study was conducted on 106 patients with spinal fractures complicated with spinal cord injury admitted to Xingtai General Hospital of North China Healthcare Group between March 2023 and June 2024, forming the spinal cord injury group. And 98 patients with isolated spinal fractures served as the fracture group. Patients in the spinal cord injury group were further categorized based on the American Spinal Injury Association(ASIA) injury scale into incomplete injury(ASIA grades B, C, and D, n=67 cases) and complete injury(ASIA grade A, n=39 cases). Based on changes in ASIA classification at 3 months postoperatively compared to admission, patients in the spinal cord injury group were classified into an improvement group(75 cases) and a worsening group(31 cases). Additionally, 72 patients with spinal fractures complicated with spinal cord injury admitted to Hebei University Affiliated Hospital during the same period were selected as an external validation group, comprising 51 patients in the improvement group and 21 in the worsening group. Clinical data were collected from all study subjects(spinal cord injury group, fracture group, and external validation group), including age, sex, medical history, cause of injury, and fracture location. Additionally, patients in the spinal cord injury group were also collected for data such as whether the injury was multisegmental, rate of spinal canal encroachment, nature of the spinal cord injury, time from injury to surgery, and time from injury to administration of corticosteroids(methylprednisolone). Fasting venous blood was collected early in the morning prior to surgery. Serum miR-22-3p and miR-210 levels were measured using real-time quantitative reverse transcription PCR(RT-qPCR). Differences in serum miRNA levels between groups were compared. Spearman′s correlation analysis was performed to assess the relationship between serum miR-22-3p, miR-210 levels and the type of spinal cord injury(complete/incomplete) in the spinal cord injury group; Pearson correlation analysis was performed to examine the relationship between miR-22-3p and miR-210 in the spinal cord injury group; Logistic regression was used to analyze risk factors for prognosis; Receiver operating characteristic(ROC) curves were used to evaluate the predictive performance of serum miR-22-3p and miR-210 for prognosis, with area under the curve(AUC) comparisons performed using the DeLong test. The predictive model built based on the training group was validated in the external validation group to assess its discriminatory ability. Results: The spinal cord injury group, the fracture group, and the external validation group showed no statistically significant differences in age, gender, medical history, cause of injury, or fracture location(P>0.05). Compared with the fracture group, serum miR-22-3p levels were significantly elevated and miR-210 levels were significantly reduced in the external validation group and the spinal cord injury group(P<0.05). Compared with the incomplete injury group, serum miR-22-3p levels were significantly elevated in the complete injury group(1.52±0.33 vs 1.19±0.25), while miR-210 levels were significantly reduced(0.61±0.14 vs 0.83±0.18)(P<0.05). Spearman correlation analysis revealed that serum miR-22-3p levels in the spinal cord injury group positively correlated with the severity of spinal cord injury(r=0.511, P<0.001), while miR-210 levels negatively correlated with the severity of spinal cord injury(r=-0.487, P<0.05). Pearson correlation analysis revealed a negative correlation between miR-22-3p and miR-210(r=-0.460, P<0.05). In the worsening group, the proportion with a spinal canal encroachment rate of ≥50%(58.06% vs 34.67%) and the proportion with a time from injury to steroid administration(methylprednisolone) of ≥8h(61.29% vs 38.67%) and serum miR-22-3p levels(1.62±0.32 vs 1.18±0.26) were all significantly higher than those in the improvement group, while serum miR-210 levels were significantly lower than those in the improvement group(0.58±0.12 vs 0.82±0.17)(P<0.05). Multivariate logistic regression analysis revealed that a spinal canal encroachment rate of ≥50%, a time from injury to steroid administration(methylprednisolone) of ≥8h, elevated miR-22-3p levels, and elevated miR-210 levels were risk factors affecting prognosis(P<0.05). ROC analysis showed that the AUC for the combined prediction was significantly higher than that for miR-22-3p(Z=2.052, P=0.040) and miR-210(Z=1.994, P=0.046) when tested individually. In the external validation, the AUC of the combined prediction was 0.919, with a sensitivity of 76.19% and a specificity of 96.08%. Conclusions: Patients with spinal fractures complicated with spinal cord injury exhibit significantly reduced serum miR-210 levels and markedly elevated serum miR-22-3p levels, both of which correlate with the severity of spinal cord injury. Combined detection of these two markers demonstrates high predictive value for patient outcomes.