Anand Swati, Young SydneyA, Esplin M Sean, Peaden Benjamin, Tolley H Dennis, Porter T Flint, Varner Michael W, D'Alton Mary E, Jackson Bruce J, Graves Steven W
Departments of Chemistry and Biochemistry, Brigham Young University, Provo, UT.
Maternal Fetal Medicine, Intermountain Healthcare, Salt Lake City, UT Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT.
J Lipid Res. 2016 Apr;57(4):687-96. doi: 10.1194/jlr.P064451. Epub 2016 Feb 18.
Despite substantial research, the early diagnosis of preeclampsia remains elusive. Lipids are now recognized to be involved in regulation and pathophysiology of some disease. Shotgun lipidomic studies were undertaken to determine whether serum lipid biomarkers exist that predict preeclampsia later in the same in pregnancy. A discovery study was performed using sera collected at 12-14 weeks pregnancy from 27 controls with uncomplicated pregnancies and 29 cases that later developed preeclampsia. Lipids were extracted and analyzed by direct infusion into a TOF mass spectrometer. MS signals, demonstrating apparent differences were selected, their abundances determined, and statistical differences tested. Statistically significant lipid markers were reevaluated in a second confirmatory study having 43 controls and 37 preeclampsia cases. Multi-marker combinations were developed using those lipid biomarkers confirmed in the second study. The initial study detected 45 potential preeclampsia markers. Of these, 23 markers continued to be statistically significant in the second confirmatory set. Most of these markers, representing several lipid classes, were chemically characterized, typically providing lipid class and potential molecular components using MS(2) Several multi-marker panels with areas under the curve >0.85 and high predictive values were developed. Developed panels of serum lipidomic biomarkers appear to be able to identify most women at risk for preeclampsia in a given pregnancy at 12-14 weeks gestation.
尽管进行了大量研究,但子痫前期的早期诊断仍然难以实现。现在人们认识到脂质参与了某些疾病的调节和病理生理过程。开展了鸟枪法脂质组学研究,以确定是否存在能够预测同一孕期后期子痫前期的血清脂质生物标志物。利用妊娠12 - 14周时收集的血清进行了一项探索性研究,其中包括27例无并发症妊娠的对照者和29例后来发展为子痫前期的病例。脂质通过直接注入飞行时间质谱仪进行提取和分析。选择显示出明显差异的质谱信号,确定其丰度,并测试统计学差异。在第二项验证性研究中对具有统计学意义的脂质标志物进行重新评估,该研究有43例对照者和37例子痫前期病例。利用第二项研究中确认的脂质生物标志物开发多标志物组合。初步研究检测到45个潜在的子痫前期标志物。其中,23个标志物在第二项验证组中仍具有统计学意义。这些标志物中的大多数代表几种脂质类别,通过质谱(MS(2))进行了化学表征,通常提供脂质类别和潜在的分子成分。开发了几个曲线下面积>0.85且预测价值高的多标志物组。所开发的血清脂质组学生物标志物组似乎能够在妊娠12 - 14周时识别出给定孕期中大多数有子痫前期风险的女性。