Systematic identification of spontaneous preterm birth-associated RNA transcripts in maternal plasma.

Systematic identification of spontaneous preterm birth-associated RNA transcripts in maternal plasma.
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DOI:
10.1371/journal.pone.0034328
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Leung TY
Leung TY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chim SS;Lee WS;Ting YH;Chan OK;Lee SW;Leung TY

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自发性早产(SPB,孕37周前)是围产儿死亡和发病的主要原因,但其发病机制尚不清楚。由于产前临床样本中SPB标记物的可用性有限,因此对SPB的研究受到阻碍,这些标记物可以很容易地与胎龄匹配的正常对照进行比较。我们假设SPB涉及异常的胎盘RNA表达,并且可以在分娩前母体血浆样品中检测到这种RNA转录物,可以与胎龄匹配的对照进行比较。使用基因表达微阵列分析基本上所有的人类基因,我们观察到与自然足月分娩(STB)胎盘相比,SPB胎盘中的426个探针信号变化>2.9倍。在这些探针所代表的基因中,我们观察到RNA稳定、细胞外基质结合和急性炎症反应中的功能过度表达。使用RT-定量PCR,我们观察到的某些基因的RNA浓度的差异,只有SPB和STB胎盘,但没有STB和足月择期剖宫产胎盘。值得注意的是,在胎盘微阵列信号高于阈值时观察到36种RNA转录物,这表明它们在母体血浆中检测的可能性。其中,IL 1 RL 1 mRNA在取自37名妇女的血浆样品中进行了测试。在最终给予SPB的女性中,在早产(≤32.9周)期间收集的10份血浆样本中有6份(60%)被检测到,但在匹配的孕周期间从没有早产的女性中收集的27份样本中仅1份(4%)被检测到(Fisher精确检验,p = 0.00056)。  我们已经确定了36 SPB相关的RNA转录,这是可能在母体血浆中检测。我们已经说明,IL 1 RL 1 mRNA更频繁地检测到产前产妇血浆样本中收集的妇女导致SPB比孕龄匹配的对照。
Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls. Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056). We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.
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