利用血浆RNA对妊娠32周前自发性早产进行早期妊娠预测：转录组发现及一组RNA标记物的初步验证
Early pregnancy prediction of spontaneous preterm birth before 32 completed weeks of pregnancy using plasma RNA: transcriptome discovery and initial validation of an RNA panel of markers.
作者信息
Weiner C P, Dong Y, Zhou H, Cuckle H, Ramsey R, Egerman R, Buhimschi I, Buhimschi C
机构信息
Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, KS, USA.
Rosetta Signaling Laboratory, Mission Hills, KS, USA.
出版信息
BJOG. 2021 Oct;128(11):1870-1880. doi: 10.1111/1471-0528.16736. Epub 2021 May 27.
OBJECTIVE
To compare the second-trimester plasma cell-free (PCF) transcriptome of women who delivered at term with that of women with spontaneous preterm birth (sPTB) at or before 32 weeks of gestation and identify/validate PCF RNA markers present by 16 weeks of gestation.
DESIGN
Prospective case-control study.
SETTING
Academic tertiary care centre.
POPULATION
Pregnant women with known outcomes prospectively sampled.
METHODS
PCF RNAs extracted from women at 22-24 weeks of gestation (five sPTB up to 32 weeks and five at term) were hybridised to gene expression arrays. Differentially regulated RNAs for sPTB up to 32 weeks were initially selected based on P value compared with control (P < 0.01) and fold change (≥1.5×). Potential markers were then reordered by narrowness of distribution. Final marker selection was made by searching the Metacore™ database to determine whether the PCF RNAs interacted with a reported set of myometrial Preterm Initiator genes. RNAs were confirmed by quantitative reverse transcription polymerase chain reaction and tested in a second group of 40 women: 20 with sPTB up to 32 weeks (mean gestation 26.5 weeks, standard deviation ±2.6 weeks), 20 with spontaneous term delivery (40.1 ± 0.9 weeks) sampled at 16-19 weeks of gestation.
MAIN OUTCOME MEASURE
Identification of PCF RNAs predictive of sPTB up to 32 weeks.
RESULTS
Two hundred and ninety-seven PCR RNAs were differentially expressed in sPTB up to 32 weeks of gestation. Further selection retained 99 RNAs (86 mRNAs and 13 microRNAs) and five of these interacted in silica with seven Preterm Initiator genes. Four of five RNAs were confirmed and tested on the validation group. The expression of each confirmed PCF RNA was significantly higher in sPTB up to 32 weeks of gestation. In vitro study of the four mRNAs revealed higher expression in placentas of women with sPTB up to 32 weeks and the potential to interfere with myometrial quiescence.
CONCLUSIONS
The PCF RNA markers are highly associated with sPTB up to 32 weeks by 16 weeks of gestation.
TWEETABLE ABSTRACT
Women destined for spontaneous preterm birth can be identified by 16 weeks of gestation with a panel of maternal plasma RNAs.
目的
比较足月分娩女性与妊娠32周及以前自然早产（sPTB）女性孕中期无细胞血浆（PCF）转录组，并鉴定/验证妊娠16周时存在的PCF RNA标志物。
设计
前瞻性病例对照研究。
地点
学术性三级护理中心。
研究对象
对已知结局的孕妇进行前瞻性采样。
方法
从妊娠22 - 24周的女性（5例妊娠32周及以前的sPTB患者和5例足月分娩女性）中提取PCF RNA，并与基因表达阵列进行杂交。与对照组相比，最初根据P值（P < 0.01）和倍数变化（≥1.5倍）选择妊娠32周及以前sPTB中差异调节的RNA。然后根据分布的狭窄程度对潜在标志物进行重新排序。通过搜索Metacore™数据库确定PCF RNA是否与一组已报道的子宫肌层早产启动基因相互作用，从而进行最终的标志物选择。通过定量逆转录聚合酶链反应对RNA进行确认，并在另一组40名女性中进行测试：20例妊娠32周及以前的sPTB患者（平均孕周26.5周，标准差±2.6周），20例自然足月分娩女性（40.1±0.9周），于妊娠16 - 19周采样。
主要观察指标
鉴定预测妊娠32周及以前sPTB的PCF RNA。
结果
297种PCR RNA在妊娠32周及以前的sPTB中差异表达。进一步筛选保留了99种RNA（86种mRNA和13种microRNA），其中5种在计算机模拟中与7种早产启动基因相互作用。5种RNA中的4种得到确认并在验证组中进行测试。每种确认的PCF RNA在妊娠32周及以前的sPTB中的表达均显著更高。对4种mRNA的体外研究显示，妊娠32周及以前sPTB女性的胎盘中这些mRNA表达更高，且有可能干扰子宫肌层的静息状态。
结论
妊娠16周时，PCF RNA标志物与妊娠32周及以前的sPTB高度相关。
推文摘要
通过一组母体血浆RNA，在妊娠16周时可识别出有自然早产倾向的女性。
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