Systemic transcriptome comparison between early‐ And late‐onset pre‐eclampsia shows distinct pathology and novel biomarkers. (17th December 2020)

• Record Type: Journal Article
• Authors: Guo, Fang; Zhang, Bao; Yang, Hao; Fu, Yixi; Wang, Yaning; Huang, Jianming; Cheng, Mi; Li, Xiaobo; Shen, Zhuojian; Li, Li; He, Ping; Xiang, Andy Peng; Wang, Shuaiyu; Zhang, Hongbo
• Is Part Of: Cell proliferation. Volume 54:Number 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-17
• Subjects: Biomarkers -- Maternal blood -- Placenta -- Pre‐eclampsia -- Single‐cell RNA sequencing; Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12968
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: Pre‐eclampsia is a leading cause of morbidity and mortality during pregnancy. Although the two forms of this disorder, early‐ (EOPE) and late‐onset of pre‐eclampsia (LOPE) are different, the underlying pathology remains elusive. We aim to unravel the difference and to identify novel biomarkers for EOPE and LOPE. Materials and Methods: A complete comparison of both placental and peripheral blood transcriptomes was performed to investigate the pathology of pre‐eclampsia. Single‐cell transcriptomics of the maternal‐fetal interface were integrated to identify novel biomarkers for EOPE and LOPE which were further verified at protein or mRNA level in patients. Results: We found that the transcriptomes of placentae from EOPE, but not LOPE, were significantly different from their respective controls. Conversely, the transcriptomes of peripheral blood from LOPE were more different from their controls than EOPE. Importantly, we identified that several classical biomarkers of pre‐eclampsia were expressed specifically in extravillous trophoblast and syncytiotrophoblast and only upregulated in EOPE, suggesting they should not be applied to all pre‐eclampsia patients in general. We further identified novel biomarkers for EOPE and LOPE from differentially expressed genes (DEGs) of placental and peripheral blood, respectively. The new biomarkers EBI3, IGF2, ORMDL3, GATA2 and KIR2DL4 were experimentally verified with patient blood samples. Conclusion: Our data demonstrate distinct pathology of EOPE and LOPE, and uncover new biomarkers that can be applied in diagnosis for pre‐eclampsia. Abstract : The schematic diagram shows the distinct pathogenesis between early‐ (EOPE) and late‐onset pre‐eclampsia (LOPE). The difference between EOPE and LOPE is demonstrated at several layers, such as risk factors, signalling pathways and disease affected/causing tissues. Based on divergence of EOPE and LOPE pathogenesis, specific biomarkers can be identified and used to distinguish both diseases by testing placental secreted proteins or maternal blood cell transcripts.