Liu Q, Chen L N, Li Y M, Sun J, Wang Y X
Research Center, Gansu Provincial Maternity and Child-care Hospital (Gansu Provincial Central Hospital), Lanzhou 730050, China.
Department of Obstetrics, Gansu Provincial Maternity and Child-care Hospital (Gansu Provincial Central Hospital), Lanzhou 730050, China.
Zhonghua Fu Chan Ke Za Zhi. 2024 Aug 25;59(8):628-635. doi: 10.3760/cma.j.cn112141-20240222-00109.
To screen plasma metabolic markers in patients with unexplained recurrent spontaneous abortion (URSA) by non-target metabolomics approach. From September 2022 to May 2023, the plasma of 23 URSA pregnant women with threatened abortion who visited the outpatient clinic of Gansu Provincial Maternity and Child-care Hospital in the first trimester (URSA group) was collected, and the plasma of 22 healthy pregnant women in the first trimester who underwent prenatal examination during the same period (normal control group) was collected. Plasma metabolomics was analyzed by ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS), fold change analysis, principal component analysis and partial least square discriminant analysis were applied to screen for differential metabolites, and the metabolites and their pathways associated with URSA were screened using receiver operating characteristic (ROC) curve and pathway enrichment analysis. There were no significant differences in age, body mass index and gestational weeks between URSA and normal control group(all <0.05). Metabolomics analysis using UPLC-MS showed that a total of 526 metabolites were detected from plasma, of which 33 were found to be differential metabolites associated with URSA based on the screening standards. Six potential metabolites with large area under the curve (AUC) were identified by ROC curve analysis, including phosphatidylethanolamine (AUC=0.972, 95%: 0.920-1.000), santene hydrate (AUC=0.902, 95%: 0.786-0.982), L-leucine (AUC=0.884, 95%: 0.772-0.960), cembrene (AUC=0.881, 95%: 0.758-0.956), caffeine (AUC=0.875, 95%: 0.756-0.962), and 4-hydroxybenzoic acid propyl ester (AUC=0.864, 95%: 0.732-0.946). The AUC for the combined diagnosis of URSA by the six metabolites was 0.983 (95%: 0.929-1.000). Pathway enrichment analysis of the differential metabolites showed that the pathogenesis of URSA was associated with a variety of metabolic pathways including caffeine metabolism, glycerophospholipid metabolism, and unsaturated fatty acid biosynthesis. The plasma metabolic profiles of pregnant women with normal pregnancies versus URSA differ in early pregnancy, and six potential metabolites such as phosphatidylethanolamine, santene hydrate, L-leucine, cembrene, caffeine, 4-hydroxybenzoic acid propyl ester, and their metabolic pathways may be involved in the pathogenesis of URSA.
采用非靶向代谢组学方法筛选不明原因复发性自然流产（URSA）患者的血浆代谢标志物。2022年9月至2023年5月，收集甘肃省妇幼保健院门诊就诊的23例孕早期有先兆流产的URSA孕妇（URSA组）的血浆，同时收集同期进行产前检查的22例孕早期健康孕妇（正常对照组）的血浆。采用超高效液相色谱（UPLC）联合质谱（MS）分析血浆代谢组学，应用倍数变化分析、主成分分析和偏最小二乘判别分析筛选差异代谢物，并使用受试者工作特征（ROC）曲线和通路富集分析筛选与URSA相关的代谢物及其通路。URSA组与正常对照组在年龄、体重指数和孕周方面均无显著差异（均P<0.05）。UPLC-MS代谢组学分析显示，血浆中共检测到526种代谢物，根据筛选标准发现其中33种为与URSA相关的差异代谢物。通过ROC曲线分析确定了6种曲线下面积（AUC）较大的潜在代谢物，包括磷脂酰乙醇胺（AUC=0.972，95%CI：0.920-1.000）、水合蒈烯（AUC=0.902，95%CI：0.786-0.982）、L-亮氨酸（AUC=0.884，95%CI：0.772-0.960）、西松烯（AUC=0.881，95%CI：0.758-0.956）、咖啡因（AUC=0.875，95%CI：0.756-0.962）和对羟基苯甲酸丙酯（AUC=0.864，95%CI：0.732-0.946）。这6种代谢物联合诊断URSA的AUC为0.983（95%CI：0.929-1.000）。差异代谢物的通路富集分析显示，URSA的发病机制与多种代谢通路有关，包括咖啡因代谢、甘油磷脂代谢和不饱和脂肪酸生物合成。正常妊娠孕妇与URSA孕妇在孕早期的血浆代谢谱不同，磷脂酰乙醇胺、水合蒈烯、L-亮氨酸、西松烯、咖啡因、对羟基苯甲酸丙酯等6种潜在代谢物及其代谢通路可能参与URSA的发病机制。
