Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; BioResource Research Center, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Placenta. 2020 Nov;101:215-220. doi: 10.1016/j.placenta.2020.09.068. Epub 2020 Sep 29.
Placenta accreta spectrum (PAS) disorder is a major cause of maternal and fetal morbidity, and in vitro biomarkers are highly desired in clinic. This study enrolled three phases of 186 pregnant women, including controls, PAS patients, placenta previa (PP) patients, and pre-eclamptic (PE) patients. Initial miRNA array screened 42 out of 768 serum miRNAs in the screening phase, and then validated four miRNAs by quantitative RT-PCR in the training phase and validation phase. Their performance for PAS prenatal screening was analyzed by the receiver operating characteristic (ROC) curve, sensitivity, and specificity. Data validated that four miRNAs (miR-139-3p, miR-196a-5p, miR-518a-3p, and miR-671-3p) were down-regulated in PAS group comparing with controls in three phases of subjects. Except for miR-518a-3p, the expression levels of these miRNAs also were significantly different between the PAS and the group including PP and PE. In addition, these biomarkers demonstrated modest screening efficiency, as the AUC ranged from 0.59 to 0.74, sensitivity 0.54 to 0.80, and specificity 0.62 to 0.76. However, the AUC and specificity can improve greatly (AUC 0.91, specificity 0.92) using a 'diagnostic signature' that combined the four miRNAs and four clinical parameters into one panel. GO and KEGG signaling pathway analysis indicated their target genes were involved in angiogenesis, embryonic development, cell migration and adhesion, and tumor-related pathways. In conclusion, the four miRNAs discovered in this study not only can be used for future non-invasive prenatal PAS screening, but also provide a new experimental basis for future research on PAS etiology.
胎盘部位滋养细胞肿瘤谱（PAS）疾病是产妇和胎儿发病率的主要原因，临床上非常需要体外生物标志物。本研究纳入了三个阶段的 186 名孕妇，包括对照组、PAS 患者、前置胎盘（PP）患者和子痫前期（PE）患者。在筛选阶段，初始 miRNA 阵列筛选出 768 个血清 miRNA 中的 42 个，然后在训练阶段和验证阶段通过定量 RT-PCR 验证了 4 个 miRNA。通过接收者操作特征（ROC）曲线、敏感性和特异性分析它们用于 PAS 产前筛查的性能。数据验证了在三个阶段的研究对象中，与对照组相比，PAS 组中四种 miRNA（miR-139-3p、miR-196a-5p、miR-518a-3p 和 miR-671-3p）下调。除了 miR-518a-3p，这些 miRNA 的表达水平在 PAS 组与包括 PP 和 PE 的组之间也存在显著差异。此外，这些生物标志物的筛查效率不高，AUC 范围为 0.59 至 0.74，敏感性为 0.54 至 0.80，特异性为 0.62 至 0.76。然而，使用将四种 miRNA 和四种临床参数组合成一个面板的“诊断特征”，AUC 和特异性可以大大提高（AUC 0.91，特异性 0.92）。GO 和 KEGG 信号通路分析表明，它们的靶基因参与血管生成、胚胎发育、细胞迁移和黏附以及肿瘤相关途径。总之，本研究中发现的四种 miRNA 不仅可用于未来的非侵入性产前 PAS 筛查，还为 PAS 病因学的未来研究提供了新的实验基础。
