急性脑出血患者血清E盒锌指结合蛋白1及DNA甲基化转移酶1与神经功能缺损和预后的相关性分析

Correlations of serum zinc finger E-box-binding protein 1 and DNA methyltransferase 1 with neurological deficit and prognosis in patients with acute cerebral hemorrhage

  • 摘要:
    目的 探讨急性脑出血(ACH)患者血清E盒锌指结合蛋白1(ZEB1)、DNA甲基化转移酶1(DNMTl)与神经功能缺损、预后的关系。
    方法 选取2019年7月—2022年7月本院收治的105例ACH患者为ACH组,依据ACH患者入院时美国国立卫生研究院卒中量表(NIHSS)评分将其分为轻度组(n=34)、中度组(n=41)、重度组(n=30)。根据改良Rankin量表(mRS)评分将ACH患者分为预后良好组(n=65)和预后不良组(n=40)。另纳入同期105例体检健康者为对照组。选取2021年7月—2022年7月本院诊治的45例ACH患者对构建的ACH预后模型的受试者工作特征(ROC)曲线进行验证。采用酶联免疫吸附试验检测血清ZEB1、DNMT1水平; 采用Spearman法分析ACH患者ZEB1、DNMT1水平与NIHSS评分的关系; 采用多因素Logistic回归模型分析ACH患者预后的影响因素,采用ROC曲线评估血清ZEB1、DNMT1水平对ACH患者预后的预测价值。
    结果 与对照组相比, ACH组血清ZEB1、DNMT1水平升高,差异有统计学意义(P < 0.05)。与轻度组相比,中度组和重度组ACH患者血清ZEB1、DNMT1、NIHSS评分均升高,差异有统计学意义(P < 0.05); 与中度组相比,重度组ACH患者血清ZEB1、DNMT1、NIHSS评分均升高,差异有统计学意义(P < 0.05)。Spearman分析结果显示, ACH患者血清ZEB1、DNMT1水平与NIHSS评分均呈正相关(r=0.569、0.763, P均 < 0.001)。单因素分析结果显示,与预后良好组比较,预后不良组患者NIHSS评分、血肿体积、ZEB1及DNMT1水平均升高或增大,差异有统计学意义(P < 0.05)。Logistic回归分析结果显示, ZEB1、DNMT1、NIHSS评分、血肿体积增大是ACH患者预后不良的危险因素(P < 0.05)。血清ZEB1、DNMT1预测ACH患者预后的曲线下面积(AUC)分别为0.834、0.854, ZEB1、DNMT1联合预测ACH患者预后的AUC为0.944, 灵敏度为95.0%, 特异度为86.2%。以验证组人群对预测预后的ROC曲线进行验证,结果显示AUC为0.903(95%CI: 0.854~0.951), 提示预后预测曲线具有较好的区分度。
    结论 ACH患者血清ZEB1、DNMT1水平较高,二者均与ACH患者神经功能缺损、预后显著相关,且血清ZEB1、DNMT1联合可能更有利于临床评估ACH患者预后情况。

     

    Abstract:
    Objective To investigate the correlations of serum zinc finger E-box-binding protein 1 (ZEB1) and DNA methyltransferase 1 (DNMTl) with neurological deficit and prognosis in patients with acute cerebral hemorrhage (ACH).
    Methods A total of 105 ACH patients in the authors′hospital from July 2019 to July 2022 were selected as ACH group, and they were divided into mild group (n=34), moderate group (n=41) and severe group (n=30) according to the National Institutes of Health Stroke Scale (NIHSS) score at admission. ACH patients were divided into good prognosis group (n=65) and poor prognosis group (n=40) according to the score of modified Rankin Scale (mRS). Another 105 healthy individuals with physical examination in the same period were included as control group. A total of 45 diagnosed ACH patients treated in authors′ hospital from July 2021 to July 2022 were selected to verify the constructed receiver operating characteristic (ROC) curve for predicting the prognosis of ACH. Serum ZEB1 and DNMT1 levels were detected by enzyme-linked immunosorbent assay; the Spearman method was used to analyze the relationship of ZEB1 and DNMT1 levels with the NIHSS score in ACH patients; the multivariate Logistic regression model was used to analyze the influencing factors for prognosis of ACH patients, and the ROC curve was used to evaluate the predictive value of serum ZEB1 and DNMT1 levels for the prognosis of ACH patients.
    Results Compared with the control group, serum levels of ZEB1 and DNMT1 were significantly higher in the ACH group (P < 0.05). Compared with the mild group, the ACH patients in moderate group and severe group had significant higher serum levels of ZEB1 and DNMT1 as well as NIHSS score (P < 0.05); compared with the moderate group, ACH patients in severe group had significant higher serum levels of ZEB1 and DNMT1 as well as NIHSS score (P < 0.05). Spearman analysis result showed that serum levels of ZEB1 and DNMT1 were positively correlated with NIHSS scores in ACH patients (r=0.569, 0.763, P < 0.001). Univariate analysis revealed that compared to the good prognosis group, patients in the poor prognosis group had significant higher or larger NIHSS score, hematoma volume, and serum levels of ZEB1 and DNMT1 (P < 0.05). Logistic regression analysis demonstrated that increases in ZEB1 and DNMT1, NIHSS score, and hematoma volume were the risk factors for poor prognosis in ACH patients (P < 0.05). Values of area under the curve (AUC) of serum ZEB1 and DNMT1 iin predicting prognosis of ACH patients were 0.834 and 0.854 respectively, and the AUC of ZEB1 combined with DNMT1 for prediction of prognosis of ACH patients was 0.944, with sensitivity of 95.0% and specificity of 86.2%. The ROC curve for predicting prognosis was validated by the validation group, and the results showed the AUC was 0.903 (95%CI, 0.854 to 0.951), indicating that the prognosis prediction curve has good discrimination.
    Conclusion The levels of serum ZEB1 and DNMT1 are high in patients with ACH, both of which are significantly related to neurological defect and prognosis in patients with ACH. The combination of serum ZEB1 and DNMT1 may be more helpful for clinical evaluation of prognosis in patients with ACH.

     

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