A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles-derived transcriptomic biomarkers in early-onset preeclampsia.
A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles-derived transcriptomic biomarkers in early-onset preeclampsia.
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DOI：
10.3389/fcvm.2023.1291642
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发表时间：
2023
影响因子：
3.6
通讯作者：
Vatish, Manu
中科院分区：
文献类型：
--
作者：
Awoyemi, Toluwalase;Zhang, Wei;Rahbar, Maryam;Cribbs, Adam;Logenthiran, Prasanna;Jiang, Shuhan;Collett, Gavin;Cerdeira, Ana Sofia;Vatish, Manu
关键词：
子痫前期（PE）是一种妊娠特异性高血压疾病，影响全球2%-8%的妊娠。该疾病的生物标志物是存在的，但虽然这些生物标志物具有很好的阴性预测值，但其阳性预测值却很差。胎盘释放到母体循环中的细胞外囊泡，即合体滋养细胞膜细胞外囊泡（STB-EVs），已被确定与PE有关，具有液体活检的潜力。本研究的目的是确定胎盘和STB-EVs转录组在子痫前期和正常妊娠（NP）之间的差异及其机制途径。我们对胎盘组织、PE （n = 6）和NP （n = 6）的中/大和小stb - ev进行了rna测序，然后进行生物信息学分析，以确定未来可用于基于ev的先兆子痫诊断测试的靶标。一些鉴定的生物标志物通过实时聚合酶链反应进行了验证。我们的分析确定了PE和NP之间STB-EV转录组的差异。随后，我们鉴定并验证了FLNB、COL17A1、SLC45A4、LEP、HTRA4、PAPP-A2、EBI3、HSD17B1、FSTL3、INHBA、SIGLEC6和CGB3的差异表达。我们的分析还通过基于stb - ev的机制途径的计算机预测确定了有趣的机制过程。在这项研究中，通过对PE中三个相关样本亚型的差异表达/携带基因的综合分析，我们确定了PE病理生理学中可能重要的潜在生物标志物和机制基因途径，并可以在未来的研究中进一步探索。
Preeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%–8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles (STB-EVs), have been identified as being involved in PE with the potential to act as liquid biopsies. The objective of this study was to identify the difference in the transcriptome of placenta and STB-EVs between preeclampsia and normal pregnancy (NP) and mechanistic pathways. We performed RNA-sequencing on placental tissue, medium/large and small STB-EVs from PE (n = 6) and NP (n = 6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions. Our analysis identified a difference in the transcriptomic STB-EV cargo between PE and NP. We then identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in silico prediction of STB-EV-based mechanistic pathways. In this study, using comprehensive profiling of differentially expressed/carried genes of three linked sample subtypes in PE, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies.
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通讯作者：
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