子痫前期患者血清VEGF、PAPP-A水平与妊娠结局的相关性研究

Correlation between serum levels of VEGF and PAPP-A and pregnancy outcomes in patients with preeclampsia

摘要:

目的 探讨子痫前期（PE）患者血清血管内皮生长因子（VEGF）、妊娠相关蛋白A（PAPP-A）水平与妊娠结局的相关性。方法 选取2020年3月—2023年3月海南现代妇女儿童医院收治的100例PE患者，根据病情程度分为PE组（68例）和重度PE组（32例），另取该院同期体检无妊娠期高血压疾病的孕妇40例作为对照组。收集资料和检测血清VEGF、PAPP-A、CC趋化因子配体17（CCL17）水平和叉头盒蛋白A1（FOXA1）、HIPK3相对表达量；采用多因素逐步Logistic回归模型分析影响PE患者妊娠结局的危险因素。结果 根据不同妊娠结局将100例PE患者分为结局不良组（38例）和结局良好组（62例）。对照组血清VEGF、CCL17、FOXA1 mRNA、HIPK3均高于PE组和重度PE组（P <0.05），PAPP-A水平低于PE组和重度PE组（P <0.05）；PE组血清VEGF、CCL17、FOXA1 mRNA、HIPK3高于重度PE组（P <0.05），PAPP-A水平低于重度PE组（P <0.05）。结局良好组血清VEGF、CCL17、FOXA1 mRNA、HIPK3均高于结局不良组（P <0.05），PAPP-A水平低于结局不良组（P <0.05）。多因素逐步Logistic回归分析结果显示，VEGF水平［O^R=1.942（95% CI：1.376，2.741）］、PAPP-A水平［O^R=2.073（95% CI：1.405，3.059）］、CCL17水平［O^R=2.145（95% CI：1.432，3.213）］、FOXA1 mRNA ［O^R=1.878（95% CI：1.352，2.609）］和HIPK3 ［O^R=1.793（95% CI：1.284，2.504）］是影响PE患者妊娠结局的独立因素（P <0.05）。ROC曲线分析结果显示，血清VEGF、PAPP-A、CCL17、FOXA1 mRNA、HIPK3预测PE患者妊娠结局的临界值分别为260.050 pg/mL、735.250 μg/mL、426.505 ng/L、0.655和0.415，敏感性分别为67.7%（95% CI：0.593，0.726）、69.4%（95% CI：0.631，0.743）、62.9%（95% CI：0.584，0.695）、75.8%（95% CI：0.714，0.803）和88.7%（95% CI：0.815，0.911），特异性分别为86.8%（95% CI：0.822，0.913）、63.2%（95% CI：0.575，0.695）、86.8%（95% CI：0.823，0.927）、94.1%（95% CI：0.908，0.981）和97.4%（95% CI：0.943，0.994）。Spearman相关性分析结果显示，血清VEGF、CCL17、FOXA1 mRNA、HIPK3与PE患者病情程度均呈负相关（r_s =-0.374、-0.512、-0.435和-0.511，均P <0.05），血清VEGF、CCL17、FOXA1 mRNA、HIPK3与PE患者妊娠结局均呈负相关（r_s =-0.412、-0.446、-0.463和-0.492，均P <0.05），血清PAPP-A水平与PE患者病情程度、妊娠结局均呈正相关（r_s =0.487和0.503，均P <0.05）。结论 PE患者血清VEGF、PAPP-A、CCL17、FOXA1 mRNA、HIPK3均呈异常表达，并与病情程度、妊娠结局相关，且对妊娠结局有一定预测价值。

Abstract:

Objective To explore the relationship between serum levels of vascular endothelial growth factor (VEGF) and pregnancy-associated plasma protein A (PAPP-A) and pregnancy outcomes in patients with preeclampsia (PE).Methods A total of 100 PE patients admitted to Hainan Modern Women and Children's Hospital from March 2020 to March 2023 were selected and divided into a PE group (n = 68) and a severe PE group (n = 32) based on the disease severity. Additionally, 40 pregnant women without hypertensive disorders of pregnancy undergoing health checkup during the same period were selected as the control group. The data were collected and serum levels of VEGF, PAPP-A, C-C motif chemokine ligand-17 (CCL17) as well as relative expression levels of forkhead box protein A1 (FOXA1) and HIPK3 were detected. The multivariable stepwise Logistic regression model was used to identify the risk factors for poor pregnancy outcomes in PE patients.Results According to different pregnancy outcomes, 100 PE patients were divided into a poor outcome group (n = 38) and a good outcome group (n = 62). The serum levels of VEGF and CCL17 and expressions of FOXA1 mRNA and HIPK3 were higher, and the serum level of PAPP-A was lower in the control group than those in the PE group and the severe PE group (P < 0.05). The serum levels of VEGF and CCL17 and expressions of FOXA1 mRNA and HIPK3 were higher, and the serum level of PAPP-A was lower in the PE group than those in the severe PE group (P < 0.05). The serum levels of VEGF and CCL17 and expressions of FOXA1 mRNA and HIPK3 were higher, and the serum level of PAPP-A was lower in the good outcome group than those in the poor outcome group (P < 0.05). The multivariable stepwise Logistic regression analysis showed that levels of VEGF [O^R = 1.942 (95% CI: 1.376, 2.741) ], PAPP-A [O^R = 2.073 (95% CI: 1.405, 3.059) ], CCL17 [O^R = 2.145 (95% CI: 1.432, 3.213) ], FOXA1 mRNA [O^R = 1.878 (95% CI: 1.352, 2.609) ], and HIPK3 [O^R = 1.793 (95% CI: 1.284, 2.504) ] were independent factors contributing to poor pregnancy outcomes in PE patients (P < 0.05). The receiver operating characteristic (ROC) curve analysis exhibited that cut-off values of serum levels of VEGF, PAPP-A and CCL17 and expressions of FOXA1 mRNA and HIPK3 for predicting adverse pregnancy outcomes in PE patients were 260.050 pg/mL, 735.250 μg/mL, 426.505 ng/L, 0.655 and 0.415, with the sensitivities being 67.7% (95% CI: 0.593, 0.726), 69.4% (95% CI: 0.631, 0.743), 62.9% (95% CI: 0.584, 0.695), 75.8% (95% CI: 0.714, 0.803) and 88.7% (95% CI: 0.815, 0.911), and the specificities being 86.8% (95% CI: 0.822, 0.913), 63.2% (95% CI: 0.575, 0.695), 86.8% (95% CI: 0.823, 0.927), 94.1% (95% CI: 0.908, 0.981) and 97.4% (95% CI: 0.943, 0.994), respectively. Spearman correlation analysis demonstrated that serum levels of VEGF and CCL17 and expressions of FOXA1 mRNA and HIPK3 were negatively correlated with the disease severity (r_s = -0.374, -0.512, -0.435 and -0.511, all P < 0.05) and pregnancy outcomes (r_s = -0.412, -0.446, -0.463 and -0.492, all P < 0.05) of PE patients, and the serum level of PAPP-A was significantly correlated with the disease severity and pregnancy outcomes of PE patients (r_s =0.487 and 0.503, both P < 0.05).Conclusions The serum levels of VEGF, PAPP-A and CCL17 as well as the expressions of FOXA1 mRNA and HIPK3 are aberrant in PE patients, and are significantly correlated with the disease severity and the pregnancy outcome. Besides, they are of certain predictive value for pregnancy outcomes.