Zhao Shenglong, Yin Chenghong, Zhai Yanhong, Jia Zhaoxia, Su Shaofei, Lu Yifan, Meng Lanlan, Li Chunbo, Liu Xiang, Cong Yuting, Li Youran, Liu Ying, Chen Lu, Wang Jing, Xu Zhengwen, Zheng Yuanyuan, Sun Zhi, Luo Ruben Y, Yu Xiaobo, Yang He S, Liu Xiaowei, Zhao Zhen, Cao Zheng
Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
Front Cardiovasc Med. 2022 Oct 11;9:946433. doi: 10.3389/fcvm.2022.946433. eCollection 2022.
Reliable biomarkers are needed to improve preeclampsia (PE) prediction accuracy. With the investigational tool of peptidomics, we aimed to identify and validate potential serum peptide biomarkers in cohorts suspected for PE development in middle or late pregnancy.
Totally 195 serum samples were prospectively collected from pregnant women with PE-related syndromes who were followed up for PE development until delivery. Serum peptidomic analysis was performed in the discovery cohort of 115 samples using matrix-assisted laser desorption ionization-time of flight coupled with Linear Trap Quadropole Orbitrap mass spectrometry. The candidate biomarkers were further validated using an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method in an independent validation cohort of 80 serum samples.
We identified 8 peptides that were differentially expressed and originated from fibrinogen alpha chain (FGA), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and complement component 3. In the subsequent LC-MS/MS quantitation analysis, the levels of the three peptides (FGA-1033.4, ITIH4-2026.9, ITIH4-2051.1) exhibited a significant difference between the PE-positive and PE-negative groups. Further, the three-peptide panel yielded an area under the ROC curve (AUC) of 0.985 [95% confidence interval (CI) 0.965-1.000] and 0.923 (95% CI 0.845-1.000) in the discovery and validation cohorts respectively, with negative predictive values of 98.1-98.8% and positive predictive values of 73.1-85.3% that were much improved when compared with that of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio.
We have discovered and validated a novel three-peptide biomarker panel predictive for the occurrence PE in pregnant women.
需要可靠的生物标志物来提高子痫前期（PE）的预测准确性。借助肽组学这一研究工具，我们旨在识别并验证妊娠中期或晚期疑似发生PE的队列中的潜在血清肽生物标志物。
前瞻性地收集了195例患有PE相关综合征的孕妇的血清样本，并对其进行随访直至分娩，观察PE的发生情况。使用基质辅助激光解吸电离飞行时间质谱仪与线性离子阱四极杆轨道阱质谱联用技术，对115份样本的发现队列进行血清肽组学分析。使用自行开发的液相色谱串联质谱（LC-MS/MS）方法，在80份血清样本的独立验证队列中进一步验证候选生物标志物。
我们鉴定出8种差异表达的肽，它们分别源自纤维蛋白原α链（FGA）、间α胰蛋白酶抑制剂重链H4（ITIH4）和补体成分3。在随后的LC-MS/MS定量分析中，三种肽（FGA-1033.4、ITIH4-2026.9、ITIH4-2051.1）的水平在PE阳性组和PE阴性组之间存在显著差异。此外，在发现队列和验证队列中，三联肽检测的曲线下面积（AUC）分别为0.985 [95%置信区间（CI）0.965-1.000]和0.923（95%CI 0.845-1.000），阴性预测值为98.1%-98.8%，阳性预测值为73.1%-85.3%，与可溶性fms样酪氨酸激酶-1/胎盘生长因子（sFlt-1/PlGF）比值相比有显著提高。
我们发现并验证了一种可预测孕妇发生PE的新型三联肽生物标志物组合。
