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

English Keywords:Spinal fracture  Spinal cord injury  MicroRNA-22-3p  MicroRNA-210  Prognosis

English Abstract:

  【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.