Miura Kiyonori, Higashijima Ai, Murakami Yuko, Fuchi Naoki, Tsukamoto Ozora, Abe Shuhei, Hasegawa Yuri, Miura Shoko, Masuzaki Hideaki
1 Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Reprod Sci. 2017 Jan;24(1):148-155. doi: 10.1177/1933719116653837. Epub 2016 Sep 27.
The aim of this study was to clarify the association between circulating pregnancy-associated, placenta-specific microRNAs (miRNAs) in maternal plasma and placental abruption. All samples were obtained after receiving written informed consent, and the study protocol was approved by the institutional review board. Maternal blood samples (7 mL) were obtained at 25 to 40 weeks of gestation from 15 cases of placental abruption (placental abruption group) and from 24 cases of uncomplicated pregnancies (uncomplicated pregnancy group). The plasma concentrations of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) were measured by quantitative real-time reverse transcription-polymerase chain reaction. There were no significant differences in clinical characteristics between the 2 groups. The median concentration of plasma cell-free miR-517c in the placental abruption group was 21 672.2 copies/mL, whereas that in the uncomplicated pregnancy group was 13 452.0 copies/mL (Mann-Whitney U test, P = .047). Receiver operating characteristic curve analysis revealed that plasma cell-free miR-517c levels discriminated placental abruption from uncomplicated pregnancy with an area under the curve of 0.692. When a cutoff negative/positive value of 15 669.6 copies/mL was selected, the sensitivity and specificity were 73.3% and 62.5%, respectively. In addition, the positive and negative predictive values were 55.0% and 78.9%, respectively. Plasma cell-free miR-517a and miR-517c levels in the large abruption (degree of abruption ≥50% of placenta) group were significantly higher than in the small abruption (<50%) group ( P = .03 for both miRNAs). In conclusion, the circulating level of cell-free miR-517c in maternal plasma was increased as a consequence of placental abruption and may be a potential biomedical marker for placental abruption.
本研究的目的是阐明孕妇血浆中循环的妊娠相关胎盘特异性微小RNA（miRNA）与胎盘早剥之间的关联。所有样本均在获得书面知情同意后采集，研究方案经机构审查委员会批准。在妊娠25至40周时，从15例胎盘早剥患者（胎盘早剥组）和24例无并发症妊娠患者（无并发症妊娠组）采集母体血样（7 mL）。通过定量实时逆转录-聚合酶链反应测量妊娠相关胎盘特异性miRNA（miR-515-3p、-517a、-517c和-518b）的血浆浓度。两组的临床特征无显著差异。胎盘早剥组血浆游离miR-517c的中位浓度为21 672.2拷贝/mL，而无并发症妊娠组为13 452.0拷贝/mL（曼-惠特尼U检验，P = 0.047）。受试者工作特征曲线分析显示，血浆游离miR-517c水平区分胎盘早剥与无并发症妊娠的曲线下面积为0.692。当选择截断阴性/阳性值为15 669.6拷贝/mL时，敏感性和特异性分别为73.3%和62.5%。此外，阳性和阴性预测值分别为55.0%和78.9%。大胎盘早剥（胎盘早剥程度≥胎盘的50%）组的血浆游离miR-517a和miR-517c水平显著高于小胎盘早剥（<50%）组（两种miRNA的P值均为0.03）。总之，胎盘早剥导致孕妇血浆中游离miR-517c的循环水平升高，其可能是胎盘早剥的潜在生物医学标志物。
