Department of Obstetrics and Gynecology, Maternal Fetal Medicine Division, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Obstetrics and Gynecology, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara 06230, Turkey.
Int J Mol Sci. 2024 Sep 26;25(19):10333. doi: 10.3390/ijms251910333.
Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography-mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features were significantly altered in EP plasma ( < 0.05). Molecular networking and metabolite identification was employed using the Global Natural Products Social Molecular Networking (GNPS) database, which identified 97 metabolites at a high confidence level. Top significant metabolites include subclasses of sphingolipids, carnitines, glycerophosphocholines, and tryptophan metabolism. The top regression model, consisting of D-erythro-sphingosine and oleoyl-carnitine, was validated in a test group and achieved an area under receiving operating curve (AUC) (95% CI) = 0.962 (0.910-1) with a sensitivity of 100% and specificity of 95.9%. Metabolite alterations indicate alterations related to inflammation and abnormal placentation in EP. The validation of these metabolite biomarkers in the future could potentially result in improved early diagnosis.
宫外孕（EP）是导致孕早期产妇发病率和死亡率的主要原因。本研究采用非靶向代谢组学方法，通过串联液相色谱-质谱法，旨在寻找可能的血浆生物标志物，用于检测输卵管妊娠。这项病例对照研究前瞻性地纳入了 50 例输卵管妊娠病例和 50 例早期宫内妊娠对照组。为了避免过度拟合，逻辑回归模型在随机选择的发现组（30 例 vs. 30 例对照组）中进行了开发，并在测试组（20 例 vs. 20 例对照组）中进行了验证。总共检测到 585 个质谱特征，其中 221 个分子特征在 EP 血浆中发生了显著改变（<0.05）。采用全球天然产物社会分子网络（GNPS）数据库进行分子网络和代谢物鉴定，鉴定出 97 种高置信度代谢物。重要的代谢物包括鞘脂类、肉碱类、甘油磷酸胆碱和色氨酸代谢物的亚类。由 D-erythro-赤藓醇和油酰肉碱组成的最佳回归模型在测试组中得到验证，曲线下面积（AUC）（95%CI）为 0.962（0.910-1），灵敏度为 100%，特异性为 95.9%。代谢物的改变表明 EP 中存在与炎症和异常胎盘形成相关的改变。这些代谢物生物标志物的未来验证可能会导致早期诊断的改善。
