Andresen Ina J, Zucknick Manuela, Degnes Maren-Helene L, Angst Martin S, Aghaeepour Nima, Romero Roberto, Roland Marie Cecilie P, Tarca Adi L, Westerberg Ane Cecilie, Michelsen Trond M
Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Oslo Centre for Biostatistics and Epidemiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Sci Rep. 2024 Dec 28;14(1):30813. doi: 10.1038/s41598-024-81277-2.
Preeclampsia is a pregnancy disorder with substantial perinatal and maternal morbidity and mortality. Pregnant women at risk of preeclampsia would benefit from early detection for follow-up, timely interventions and delivery. Several attempts have been made to identify protein biomarkers of preeclampsia, but findings vary with demographics, clinical characteristics, and time of sampling. In the current study, we combined three independent longitudinal pregnancy cohorts (Detroit, Stanford and Oslo) resulting in 124 late-onset preeclampsia (LOPE) cases and 178 gestational age matched controls, and analyzed > 1000 proteins in maternal plasma sampled between 12 and 34 weeks of gestation. Differential abundance analysis of combined protein data revealed increased deviation in protein abundance trajectories throughout gestation in women destined to develop LOPE compared to controls. There were no differentially abundant proteins at time interval T1 (12-19 weeks), yet 31 differentially abundant proteins were found at time interval T2 (19-27 weeks), and 48 proteins at time interval T3 (27- 34 weeks). Multi-protein random forest models assessed via cross-validation predicted LOPE with an area under the ROC curve of 0.72 (0.65-0.78), 0.76 (0.71-0.81) and 0.80 (0.75-0.85) at time interval T1, T2 and T3, respectively. The results at T3 were confirmed using a leave-one-cohort-out analysis suggesting cross-cohort consistency, and at T1 and T2 when the largest two cohorts were used as training sets.
子痫前期是一种具有较高围产期和孕产妇发病率及死亡率的妊娠疾病。有子痫前期风险的孕妇将受益于早期检测以便进行随访、及时干预和分娩。人们已经多次尝试识别子痫前期的蛋白质生物标志物，但研究结果因人口统计学、临床特征和采样时间而异。在本研究中，我们合并了三个独立的纵向妊娠队列（底特律、斯坦福和奥斯陆），共纳入124例晚发型子痫前期（LOPE）病例和178例孕周匹配的对照，并分析了妊娠12至34周期间采集的孕妇血浆中的1000多种蛋白质。对合并后的蛋白质数据进行差异丰度分析发现，与对照组相比，注定会发生LOPE的女性在整个妊娠期蛋白质丰度轨迹的偏差增加。在时间间隔T1（12 - 19周）时没有差异丰度的蛋白质，但在时间间隔T2（19 - 27周）时发现了31种差异丰度的蛋白质，在时间间隔T3（27 - 34周）时发现了48种蛋白质。通过交叉验证评估的多蛋白随机森林模型在时间间隔T1、T2和T3时预测LOPE的ROC曲线下面积分别为0.72（0.65 - 0.78）、0.76（0.71 - 0.81）和0.80（0.75 - 0.85）。使用留一队列分析证实了T3时的结果，表明跨队列的一致性，以及在T1和T2时将最大的两个队列用作训练集时的结果。
