基于血清外泌体miRNA-517建立子痫前期不良妊娠结局预测模型及验证

Establishment and validation of a predictive model for adverse pregnancy outcomes in preeclampsia based on the expression level of miRNA-517 in serum exosomes

目的 分析外泌体miRNA-517在子痫前期(preeclampsia, PE)孕妇血清中的表达,并建立PE不良妊娠结局的预测模型。方法 选择2021年1月至2022年12月在海南医科大学第二附属医院产科就诊的PE孕妇121例为PE组,同期产检并分娩的健康孕妇127例为对照组,比较两组血清miRNA-517、miRNA-518、miRNA-519表达水平。按不同妊娠结局将PE孕妇分为妊娠结局不良组(31例)和妊娠结局良好组(90例),采用多因素Logistic回归分析PE孕妇发生不良妊娠结局的影响因素,根据独立预测因素结合其影响权重建立列线图模型,运用R软件绘制列线图、受试者工作特征(ROC)曲线,验证列线图的预测价值。结果 (1) PE组孕妇血清miRNA-517、miRNA-518表达水平高于对照组,而血清miRNA-519表达水平低于对照组,差异有统计学意义(P<0.05)。(2)单因素分析示,妊娠结局不良组收缩压、舒张压、24 h尿蛋白定量、D-二聚体、血小板减少的比例及miRNA-517明显高于妊娠结局良好组(P<0.05)。多因素Logistic回归分析示,舒张压、D-二聚体、miRNA-517以及血小板减少为影响PE孕妇发生不良妊娠结局的独立危险因素(OR>1,P<0.05)。(3)以上述4个因素构建列线图模型并绘制的ROC曲线,AUC为0.917(95%CI:0.901-0.979,P<0.05),灵敏度94.5%,特异度90.3%,经过内部验证后模型的区分度评价指标C-Index为0.912(95%CI:0.878-0.975),拟合优度检验结果示,每个PE孕妇发生不良妊娠结局风险的预测值与实际观测值符合度良好(P>0.05)。结论 PE孕妇血清miRNA-517表达水平异常升高,基于血清miRNA-517表达构建的列线图模型对评估PE孕妇不良妊娠结局发生风险具有较好的效能。

Objective To analyze the expression of miRNA-517 in the serum of preeclampsia(PE)pregnant women and to establish a predictive model for adverse pregnancy outcomes of PE.Methods 121 PE pregnant women who received obstetric treatment at the Second Affiliated Hospital of Hainan Medical University from January 2021 to December 2022 were selected as the PE group,and 127 healthy pregnant women during the same time were selected as the control group.The expression levels of miRNA-517,miRNA-518,and miRNA-519 in the serum of patients between the two groups were compared.PE pregnant women were divided into a poor pregnancy outcome group(31 cases)and a good pregnancy outcome group(90 cases)based on different pregnancy outcomes.Multivariate Logistic regression analysis was used to analyze the influencing factors of adverse pregnancy outcomes in PE pregnant women.A column chart model was established based on independent predictive factors combined with their influence weights.R software was used to draw a column chart and a ROC curve was drawn to verify the predictive value of the column chart.Results(1)The miRNA-517 and miRNA-518 in the serum of pregnant women in the PE group were higher than those in the control group,while the miRNA-519 in the serum were significantly lower than those in the control group,the differences were statistically significant(P<0.05).(2)Univariate analysis showed that the proportion of systolic blood pressure,diastolic blood pressure,24-hour urine protein quantification,D-dimer,thrombocytopenia,and miRNA-517 of patients in the poor pregnancy outcome group were significantly higher than those in the good pregnancy outcome group(P<0.05).Multivariate Logistic analysis showed that diastolic blood pressure D-dimer,miRNA-517,and thrombocytopenia were independent risk factors for adverse pregnancy outcomes in PE pregnant women(OR>1,P<0.05).(3)A column chart model was established based on the above four factors with an AUC of 0.917(95%CI:0.901-0.979,P<0.05),with a sensitivity of 94.5%and specificity of 90.3%.The discriminability evaluation index C-Index of the model was 0.912(95%CI:0.878-0.975).The goodness of fit test results showed that the predicted risk of adverse pregnancy outcomes for each PE pregnant woman was in good agreement with the actual observed values(P>0.05).Conclusion The expression level of serum miRNA-517 in pregnant women with PE is abnormally elevated.The nomogram model is highly effective in assessing the risk of adverse pregnancy outcomes in pregnant women with PE based on the expression of serum miRNA-517.