Wang Zhiyin, Zheng Mingming, Duan Honglei, Wang Yuan, Dai Yimin, Tang Huirong, Wang Ya, Liu Dan, Cao Chenrui, Gu Ning, Weng Qiao, Zhou Yan, Zhao Guangfeng, Hu Yali
Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA, 94143, USA.
BMC Pregnancy Childbirth. 2025 Mar 19;25(1):319. doi: 10.1186/s12884-025-07424-3.
Preeclampsia is a common and severe pregnancy complication. The syndrome is highly heterogeneous, making accurate classification difficult, which is not conductive to find ways to predict and prevent this syndrome. Recently, we reported that high placental miR-155 defined a new subtype of preeclampsia. Here, we aimed to examine whether high maternal sero-miR-155 could be a marker to identify this subtype.
To explore whether the patients with high sero-miR-155 no matter in first and third trimester, we conducted a case-control and a longitudinal cohort study. We measured the sero-miR-155 levels at first, second and third trimesters in all pregnant women. Then, using the 95th percentile (P95) of sero-miR-155 in controls as the cut-off value, we divided the preeclamptic patients into high sero-miR-155 group (≥ P95) and normal sero-miR-155 group (< P95). We compared the difference of clinical manifestations between two groups and used t-distributed stochastic neighbor embedding (t-SNE) to evaluate whether the patients with high sero-miR-155 could be clustered as a subtype. Finally, we evaluated the predictive value of sero-miR-155 in the subtype.
The case-control study included 525 subjects (350 controls and 175 preeclampsia) and the longitudinal cohort study included 411 subjects (274 controls and 137 preeclampsia). Sero-miR-155 was significantly elevated in preeclampsia. Compared with preeclamptic patients with normal sero-miR-155 levels, the cases with high sero-miR-155 had significantly higher blood pressure and other severe preeclampsia-related complications. The incidences of HELLP syndrome [5.2% (5/96) vs. 0.9% (2/216), p < 0.01], visual disturbance [15.6% (15/96) vs. 4.6% (10/216), p < 0.01], hypertensive retinopathy [13.5% (13/96) vs. 3.2% (7/216), p < 0.01], and placenta abruption [7.3% (7/96) vs. 0.9% (2/216), p < 0.01] in patients with high miR-155 level were significantly increased. T-SNE analysis showed the patients with high sero-miR-155 were predominantly clustered on the left of the plot.
The patients with high sero-miR-155 exhibited more severe clinical manifestations and sero-miR-155 could be a biomarker to identify a subtype of preeclampsia with high sero-miR-155.
子痫前期是一种常见且严重的妊娠并发症。该综合征高度异质性，难以进行准确分类，这不利于找到预测和预防该综合征的方法。最近，我们报道高胎盘miR-155定义了一种新的子痫前期亚型。在此，我们旨在研究高母体血清miR-155是否可作为识别该亚型的标志物。
为探究无论在孕早期还是孕晚期血清miR-155水平高的患者情况，我们进行了一项病例对照研究和一项纵向队列研究。我们测量了所有孕妇在孕早期、孕中期和孕晚期的血清miR-155水平。然后，以对照组血清miR-155的第95百分位数（P95）作为临界值，将子痫前期患者分为高血清miR-155组（≥P95）和正常血清miR-155组（<P95）。我们比较了两组临床表现的差异，并使用t分布随机邻域嵌入（t-SNE）来评估血清miR-155水平高的患者是否可聚类为一个亚型。最后，我们评估了血清miR-155在该亚型中的预测价值。
病例对照研究纳入525名受试者（350名对照者和175名单纯子痫前期患者），纵向队列研究纳入411名受试者（274名对照者和137名单纯子痫前期患者）。子痫前期患者的血清miR-155显著升高。与血清miR-155水平正常的子痫前期患者相比，血清miR-155水平高的患者血压显著更高，且有其他更严重的子痫前期相关并发症。高miR-155水平患者的HELLP综合征发生率[5.2%（5/96）对0.9%（2/216），p<0.01]、视觉障碍发生率[15.6%（15/96）对4.6%（10/216），p<0.01]、高血压性视网膜病变发生率[13.5%（13/96）对3.2%（7/216），p<0.01]和胎盘早剥发生率[7.3%（7/96）对0.9%（2/216），p<0.01]均显著增加。t-SNE分析显示血清miR-155水平高的患者主要聚集在图的左侧。
血清miR-155水平高的患者表现出更严重临床表现，且血清miR-155可能是识别血清miR-155水平高的子痫前期亚型的生物标志物。
