重型颅脑损伤血清EZH2和DKK1变化及其临床意义

Changes and clinical significance of serum enhancer of zeste homolog 2 and Dickkopf-related protein 1 in patients with severe craniocerebral injury

目的:探讨Zeste同源物增强子2(EZH2)和Dickkopf相关蛋白1(DKK1)在重型颅脑损伤患者血清中变化及临床意义。方法:选取2021年6月至2022年10月在遂宁市中心医院接受治疗的160例重型颅脑损伤患者为观察组及165例健康体检志愿者为对照组。以格拉斯哥昏迷评分(GCS)分重型组75例,特重型组85例。酶联免疫吸附法检测患者重型颅脑损伤后第1、3、7天血清EZH2、DKK1水平(对照组为入组第1天)。两组间比较行t检验;Logistic回归分析影响患者预后的因素;受试者工作特征曲线分析血清中EZH2、DKK1水平对患者预后的预测价值。结果:观察组患者血清EZH2水平低于对照组[(11.28±3.45)μg/L比(25.23±5.87)μg/L,t=26.017,P<0.05],DKK1水平高于对照组[(610.80±126.32)μg/L比(178.94±54.76)μg/L,t=40.194,P<0.05];特重型组患者血清EZH2水平低于重型组[(8.54±2.72)μg/L比(14.38±4.28)μg/L,t=10.421,P<0.05],DKK1水平高于重型组[(821.06±159.02)μg/L比(385.84±89.26)μg/L,t=20.962,P<0.05]。第3天重型组与特重型组患者血清EZH2水平均高于第1、7天[(19.45±5.79)μg/L比(14.38±4.28)、(15.25±4.47)μg/L,t=6.098、4.973,P<0.05;(14.01±4.04)μg/L比(8.54±2.72)、(9.98±3.19)μg/L,t=10.355、7.218,P<0.05],第3天重型组与特重型组患者DKK1水平均低于第1、7天[(271.81±72.21)μg/L比(385.84±89.26)、(345.54±84.21)μg/L,t=8.601、5.756,P<0.05;(576.45±101.50)μg/L比(821.06±159.02)、(757.21±141.49)μg/L,t=11.954、9.571,P<0.05];良好组患者血清EZH2水平明显降低于预后不良组[(7.27±2.35)μg/L比(13.27±3.95)μg/L,t=9.959,P<0.05],DKK1水平高于预后不良组[(798.02±198.81)μg/L比(525.70±93.37)μg/L,t=11.812,P<0.05]。第3天预后良好组与预后不良组患者血清EZH2水平均高于第1、7天[(18.46±5.56)μg/L比(13.27±3.95)、(14.36±4.36)μg/L,t=7.981、6.086,P<0.05;(12.38±3.32)μg/L比(7.27±2.35)、(8.25±2.54)μg/L,t=8.883、6.986,P<0.05],第3天预后良好组与预后不良组患者DKK1水平均低于第1、7天[(381.19±82.17)μg/L比(525.70±93.37)、(485.24±85.74)μg/L,t=17.377,12.512,P<0.05;(549.06±100.09)μg/L比(798.02±198.81)、(738.04±178.22)μg/L,t=10.693,8.117,P<0.05];GCS评分高[比值比(OR)=0.872,P<0.05]、高水平EZH2(OR=0.515,P<0.05)是影响患者预后的保护因素,高水平DKK1(OR=1.013,P<0.05)是影响患者预后的危险因素;EZH2、DKK1联合预测患者预后的曲线下面积为0.965[95%可信区间(CI):0.939~0.991],均优于其各自单独预测(Z两者联合-EZH2=1.930,P<0.05;Z两者联合-DKK1=2.663,P<0.05)。结论:重型颅脑损伤患者血清EZH2水平随时间先升高再降低,DKK1水平先降低再升高,均与患者病情严重程度及预后明显相关。

Objective To investigate the changes and clinical significance of enhancer of zeste homolog 2(EZH2)and Dickkopf-related protein 1(DKK1)in serum of patients with severe craniocerebral injury.Methods A total of 160 patients with severe craniocerebral injury who were treated in suining central hospital from June 2021 to October 2022 were selected as the observation group,and 165 healthy volunteers were selected as the control group.According to Glasgow coma scale(GCS),the patients were divided into severe group(75 cases)and extra severe group(85 cases).Enzyme linked immunosorbent assay was used to detect the levels of EZH2 and DKK1 in the serum of patients on the first,third and seventh days(the control group on the first day of enrollment).T-test was used for inter-group data;Logistic regression was used to analyze the factors affecting the prognosis of patients;ROC curve was used to analyze the prognostic value of serum EZH2 and DKK1 levels in patients.Results The serum EZH2 level of patients in the observation group was lower control group[(11.28±3.45)μg/L vs.(25.23±5.87)μg/L,t=26.017,P<0.05],DKK1 level was higher control group[(610.80±126.32)μg/L vs.(178.94±54.76)μg/L,t=40.194,P<0.05];the serum EZH2 level of patients in the severe group was lower severe group[(8.54±2.72)μg/L vs.(14.38±4.28)μg/L,t=10.421,P<0.05],DKK1 level was higher severe group[(798.02±198.81)μg/L vs.(525.70±93.37)μg/L,t=11.812,P<0.05].The serum EZH2 level in patients with severe type and extra severe type on the third day were higher than those on the first and seventh days[(19.45±5.79)μg/L vs.(14.38±4.28),(15.25±4.47)μg/L,t=6.098,4.973,P<0.05;(14.01±4.04)μg/L vs.(8.54±2.72),(9.98±3.19)μg/L,t=10.355,7.218,P<0.05],the DKK1 level in the severe group and the extra severe group on the third day was lower than that on the first and seventh days[(271.81±72.21)μg/L vs.(385.84±89.26),(345.54±84.21)μg/L,t=8.601,5.756,P<0.05;(576.45±101.50)μg/L vs.(821.06±159.02),(757.21±141.49)μg/L,t=11.954,9.571,P<0.05];the serum EZH2 level in poor prognosis group was lower than that in good prognosis group[(7.27±2.35)μg/L vs.(13.27±3.95)μg/L,t=9.959,P<0.05],and DKK1 level was higher good prognosis group[(98.02±198.81)μg/L vs.(525.70±93.37)μg/L,t=11.812,P<0.05].The serum EZH2 level of patients in good prognosis group and poor prognosis group on the third day were higher than those on the first and seventh days[(8.46±5.56)μg/L vs.(13.27±3.95),(14.36±4.36)μg/L,t=7.981,6.086,P<0.05;(12.38±3.32)μg/L vs.(7.27±2.35),(8.25±2.54)μg/L,t=8.883,6.986,P<0.05],and DKK1 level of patients in good prognosis group and poor prognosis group on the third day were lower than those on the first and seventh days[(381.19±82.17)μg/L vs.(525.70±93.37),(485.24±85.74)μg/L,t=17.377,12.512,P<0.05;(549.06±100.09)μg/L vs.(798.02±198.81),(738.04±178.22)μg/L,t=10.693,8.117,P<0.05];high GCS score[odds ratio(OR)=0.872,P<0.05]and high levels of EZH2(OR=0.515,P<0.05)were protective factors affecting the prognosis of patients,and high levels of DKK1(OR=1.013,P<0.05)was a risk factor affecting the prognosis of patients;the area under the curve of EZH2 combined with DKK1 to predict the prognosis of patients was 0.965[95%confidence interval(CI):0.939-0.991],which was better than their independent prediction(Zcombination-EZH2=1.930,P<0.05;Zcombination-DKK1=2.663,P<0.05).Conclusion The serum EZH2 level in patients with severe craniocerebral injury increases first and then decreases with time,DKK1 level decreases first and then increases,they are related to the severity and prognosis of the patient.