MicroRNA-148a在妊娠期肝内胆汁淤积症中的表达及临床预测价值

Expression and clinical predictive value of microRNA-148a in intrahepatic cholestasis of pregnancy

摘要:

目的 探讨microRNA-148a在妊娠期肝内胆汁淤积症（ICP）中的表达及临床预测价值。方法 选取2020年2月—2022年1月天水市中西医结合医院收治的113例ICP患者作为ICP组，另选取同期在该院产检的80例健康孕妇作为对照组。对比两组肝功能及microRNA-148a相对表达量。随访统计ICP患者妊娠结局，并依据妊娠结局分为不良组和良好组。对比不同妊娠结局ICP患者临床资料及microRNA-148a相对表达量。多因素逐步Logistic回归模型分析影响ICP患者妊娠结局的相关因素。绘制受试者工作特征（ROC）曲线，以曲线下面积（AUC）分析microRNA-148a对ICP患者妊娠结局的预测效能。结果 ICP组总胆红素（TBIL）、直接胆红素（DBIL）、门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）及microRNA-148a相对表达量高于对照组（P <0.05）。不良组与良好组年龄、体质量指数、孕周、产次构成、DBIL、AST、ALT、白细胞计数、血小板计数、平均血小板体积、血红蛋白、尿蛋白、血肌酐比较，差异均无统计学意义（P >0.05）。不良组重度ICP病情占比高于良好组，TBA、TBIL、microRNA-148a相对表达量高于良好组（P <0.05）。多因素逐步Logistic回归分析结果显示：重度ICP病情［O^R=2.875（95% CI：1.093，7.559）］、microRNA-148a高表达［O^R=3.343（95% CI：1.272，8.791）］均为影响ICP孕妇预后的危险因素（P <0.05）。ROC曲线分析结果显示，血清microRNA-148a预测ICP孕妇妊娠结局的最佳截断值为1.12，敏感性、特异性及曲线下面积分别为72.73%（95% CI：0.496，0.884）、81.32%（95% CI：0.715，0.884）、0.798（95% CI：0.712，0.868）。结论 microRNA-148a在ICP患者中高表达，且血清microRNA-148a对ICP患者妊娠结局的预测效能较高。

Abstract:

Objective To investigate the expression and clinical predictive value of microribonucleic acid-148a (microRNA-148a) in intrahepatic cholestasis of pregnancy (ICP).Methods A total of 113 ICP patients admitted to our hospital from February 2020 to January 2022 were selected as the ICP group, and 80 healthy pregnant women who received antenatal care in the hospital during the same period were selected as the control group. The liver function and the expression level of microRNA-148a were compared between the ICP group and the control group. The pregnancy outcomes of ICP patients were followed up and analyzed, and these patients were divided into the poor group and the good group according to their pregnancy outcomes. The clinical data and the expression level of microRNA-148a of ICP patients with different pregnancy outcomes were compared. Multivariable stepwise Logistic regression analysis was performed to determine factors affecting the pregnancy outcomes in patients with ICP. The receiver operating characteristic (ROC) curves were plotted, and the areas under the ROC curves (AUCs) were employed to analyze the predictive efficacy of microRNA-148a for pregnancy outcomes in ICP patients.Results The levels of total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and microRNA-148a in the ICP group were higher than those in the control group (P < 0.05). There was no difference in the age, body mass index, gestational week, parity, levels of DBIL, AST and ALT, white blood cell count, platelet count, mean platelet volume, or levels of hemoglobin, urine protein and blood creatine (P > 0.05). The proportion of severe ICP in the poor group was higher than that in the good group (P < 0.05), and levels of TBA, TBIL and microRNA-148a in the poor group were higher than those in the good group (P < 0.05). The multivariable stepwise Logistic regression analysis showed that severe ICP [O^R = 2.875, (95% CI: 1.093, 7.559) ] and high expression level of microRNA-148a [O^R = 3.343, (95% CI: 1.272, 8.791)] were risk factors for the poor prognosis of ICP patients (P < 0.05). ROC curve analysis exhibited that the optimal cut-off value of microRNA-148a for predicting pregnancy outcomes in ICP patients was 1.12, with the sensitivity, specificity and AUC being 72.73% (95% CI: 0.496, 0.884), 81.32% (95% CI: 0.715, 0.884) and 0.798 (95% CI: 0.712, 0.868), respectively.Conclusions MicroRNA-148a is highly expressed in ICP patients, and the serum level of microRNA-148a has high predictive efficacy for pregnancy outcomes in ICP patients.