四肢骨折延迟愈合患者血清miR-206、IGF-1、sICAM-1水平变化及诊断效能

Changes in levels of serum miR-206,IGF-1,and sICAM-1 in patients with delayed healing of limb fracture and the diagnostic efficiency

目的观察四肢骨折延迟愈合患者血清微小RNA-206(miR-206)、胰岛素样生长因子-1(IGF-1)、可溶性细胞间黏附分子(sICAM-1)的水平变化,并探讨其对骨折延迟愈合的诊断效能。方法159例四肢骨折患者,行钢板内固定或髓内钉固定术,分别于术前(T0)及术后第3天(T1)、第1周(T2)、第4周(T3)时采集静脉血,实时荧光PCR法检测血清miR-206,ELISA法检测血清IGF-1、sICAM-1。术后3个月时159例患者根据是否存在骨折延迟愈合分为89例骨折延迟愈合(延迟组),70例骨折正常愈合(正常组)。采用单因素分析、Logistic逐步回归分析法分析骨折延迟愈合的危险因素。绘制受试者工作特征曲线(ROC),分析血清miR-206、IGF-1、sICAM-1及三者联合对骨折延迟愈合的诊断效能。结果T0~T3时两组血清miR-206表达、IGF-1水平逐渐增高,sICAM-1水平逐渐降低(P均<0.05)。与正常组比较,T0、T1、T2、T3时延迟组血清miR-206表达、sICAM-1水平高,血清IGF-1水平低(P均<0.05)。骨质疏松、损伤类型、T3基线时血清miR-206、T3基线时血清IGF-1、T3基线时血清sICAM-1是骨折延迟愈合的危险因素(P均<0.01)。T3基线时,血清miR-206、IGF-1、sICAM-1诊断骨折延迟愈合的截断值分别为0.62、291.34μg/L、202.43 ng/mL时,其诊断骨折延迟愈合的灵敏度分别为72.41%、79.31%、70.11%,特异度分别为72.86%、80.00%、84.29%,阳性预测值为76.83%、86.13%、77.22%,阴性预测值分别为68.00%、75.68%、66.67%,AUC分别为0.690(95%CI:0.606~0.773)、0.682(95%CI:0.596~0.767)、0.709(95%CI:0.626~0.793)。血清miR-206、IGF-1、sICAM-1联合诊断骨折延迟愈合的灵敏度、特异度、阳性预测值、阴性预测值分别为91.95%、91.43%、93.02%、90.14%,AUC为0.895(95%CI:0.837~0.95)。T3时血清miR-206、IGF-1、sICAM-1水平联合诊断骨折延迟愈合AUC高于三者单独诊断(z分别为3.021、3.162、2.615,P均<0.05)。结论手术固定患处的骨折延迟愈合患者血清miR-206、sICAM-1水平升高,IGF-1水平降低。血清miR-206、sICAM-1、IGF-1联合诊断四肢骨折患者术后骨折延迟愈合的准确性较高。

Objective To observe the changes of serum levels of micro RNA-206(miR-206),insulin-like growth factor-1(IGF-1),and soluble intercellular cell adhesion molecule(sICAM-1)in patients with delayed healing of limb fracture,and to explore their diagnostic efficacy for delayed healing of limb fracture.Methods Totally 159 patients with limb fractures were treated with plate fixation or intramedullary nail fixation.Venous blood samples were collected before operation(T0)and at 3 days(T1),1 week(T2)and 4 weeks(T3)after operation.Serum miR-206 was detected by realtime PCR,and serum IGF-1 and sICAM-1 were detected by ELISA.Three months after the operation,159 patients were divided into 89 cases of delayed fracture healing(delayed group)and 70 cases of normal fracture healing(normal group)according to the presence or absence of delayed fracture healing.Univariate analysis and Logistic stepwise regression analysis were used to analyze the risk factors of delayed fracture healing.Receiver operating characteristic(ROC)curves were drawn to analyze the diagnostic efficacy of serum miR-206,IGF-1,sICAM-1 and the combination for delayed fracture healing.Results At T0-T3,the expression of miR-206 and the level of IGF-1 increased gradually,while the level of sICAM-1 decreased gradually(all P<0.05).Compared with the normal group,the expression of miR-206 and the level of sICAM-1 were higher in the delayed group at T0,T1,T2 and T3,while the serum IGF-1 level was lower in the delayed group(all P<0.05).Osteoporosis,injury type,serum miR-206,IGF-1,and sICAM-1 at T3 baseline were risk factors for delayed fracture healing(all P<0.01).At T3 baseline,the cut-off values of miR-206,IGF-1 and sICAM-1 in diagnosing delayed fracture healing were 0.62,291.34μg/L and 202.43 ng/mL,respectively;the sensitivities of diagnosis delayed fracture healing were 72.41%,79.31%,and 70.11%,respectively,the specificities were 72.86%,80.00% and 84.29%,respectively,the positive predictive values were 76.83%,86.13% and 77.22%,the negative predictive values were 68.00%,75.68% and 66.67%,respectively,and the AUC were 0.690(95%CI:0.606-0.773),0.682(95%CI:0.596-0.767)and 0.709(95%CI:0.626-0.793),respectively.The sensitivity,specificity,positive predictive value,and negative predictive value of combined miR-206,IGF-1 and sICAM-1 in the diagnosis of delayed fracture healing were 91.95%,91.43%,93.02%,and 90.14%,respectively,and AUC was 0.895(95%CI:0.837-0.95).At T3,the AUC of serum miR-206,IGF-1,and sICAM-1 levels combined in diagnosis of delayed fracture healing was higher than that of the three alone(z=3.021,3.162,2.615,all P<0.05).Conclusion The serum levels of miR-206 and sICAM-1 increased and the level of IGF-1 decreased in patients with delayed fracture healing after surgical fixation,and the accuracy of serum miR-206,sICAM-1 and IGF-1 combined in the diagnosis of delayed fracture healing was higher.