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血浆RNA图谱揭示了妊娠期孕妇未来的健康和疾病特征
作者:小柯机器人 发布时间:2022/1/9 14:01:00

美国布里格姆妇女医院Thomas F. McElrath,美国Mirvie公司Morten Rasmussen和Michal A. Elovitz等共同合作取得重要进展。他们的研究认为血浆RNA图谱能够揭示妊娠期孕妇未来的健康和疾病特征。相关论文于2022年1月5日在线发表于《自然》杂志上。

在这里,研究人员证明了血浆中游离的RNA (cell-free RNA, cfRNA) 能够揭示正常妊娠进展模式并在临床表现前几个月识别发生子痫前期的风险。他们的研究结果集中在8个独立收集的的综合性转录组数据上,包括 1840 名不同种族的孕妇,以及2539 个储存血浆样本的回顾性分析。子痫前期数据包括来自两个不同收集组的524个样本(72个病例和452个非病例),收集于分娩前14.5周(s.d., 4.5周)。

研究人员表明,单次抽血的 cfRNA 特征可以追踪胎盘、母体和胎儿水平的妊娠进展,并且可以稳健地预测子痫前期,敏感性为 75%,阳性预测值为 32.3%( s.d., 3%),这优于目前最先进的方法。正常妊娠进展和子痫前期的 cfRNA 特征独立于临床因素,如母亲年龄、体重指数和种族,累计占模型方差的比例不到 1%。此外,子痫前期的 cfRNA 特征包含与子痫前期潜在病理生理学生物学过程相关的基因特征。

据悉,孕产妇发病率和死亡率持续上升,而子痫前期是造成这一负担的主要原因。然而,目前很难在临床表现前评估出潜在病理生理学特征,以识别怀孕的风险。

附:英文原文

Title: RNA profiles reveal signatures of future health and disease in pregnancy

Author: Rasmussen, Morten, Reddy, Mitsu, Nolan, Rory, Camunas-Soler, Joan, Khodursky, Arkady, Scheller, Nikolai M., Cantonwine, David E., Engelbrechtsen, Line, Mi, Jia Dai, Dutta, Arup, Brundage, Tiffany, Siddiqui, Farooq, Thao, Mainou, Gee, Elaine P. S., La, Johnny, Baruch-Gravett, Courtney, Santillan, Mark K., Deb, Saikat, Ame, Shaali M., Ali, Said M., Adkins, Melanie, DePristo, Mark A., Lee, Manfred, Namsaraev, Eugeni, Gybel-Brask, Dorte Jensen, Skibsted, Lillian, Litch, James A., Santillan, Donna A., Sazawal, Sunil, Tribe, Rachel M., Roberts, James M., Jain, Maneesh, Hgdall, Estrid, Holzman, Claudia, Quake, Stephen R., Elovitz, Michal A., McElrath, Thomas F.

Issue&Volume: 2022-01-05

Abstract: Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.

DOI: 10.1038/s41586-021-04249-w

Source: https://www.nature.com/articles/s41586-021-04249-w

 

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html