Yue Zu1, Sheng Guo2, Guodong Li1, Qianyan Gao1, Ximin Wang1, Chengliang Zhang1, Dong Liu1. 1. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, China. 2. The First Affiliated Hospital of Xinxiang Medical University Weihui, Henan, China.
Abstract
OBJECTIVES: Intrahepatic cholestasis of pregnancy (IHCP) causes itching, preterm birth, and stillbirth. However, there is no accurate diagnostic method for IHCP. Currently, circulating microRNAs (miRNAs) have become candidate biomarkers for the diagnosis of multiple diseases. Here, we investigated the diagnostic value of miRNAs in IHCP and aimed to predict the molecular mechanism of IHCP pathogenesis. METHODS: We analyzed differentially expressed miRNAs in both women with IHCP and normal pregnant women. The selected candidate miRNAs were validated in 46 IHCP cases and 46 normal pregnant subjects, and we constructed receiver operator characteristic curves of miRNAs. Pearson correlations between levels of total bile acid (TBA) and differentially expressed miRNAs were also calculated. In addition, we clustered functionally significant biological pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: The expression levels of 13 miRNAs were remarkably upregulated while the other 35 miRNAs were significantly downregulated, in women with IHCP (P≤0.05) when compared with healthy pregnant women. The areas under the curves of miRNA-7706, miRNA-877-3p, and miRNA-128-3p were higher than 0.90, indicating more reliable diagnosis of IHCP. The Pearson analysis showed that the levels of these miRNAs were positively correlated to TBA level. Additionally, the results of bioinformatics analysis revealed that the differentially expressed miRNAs mainly influenced fatty acid biosynthesis, the endoplasmic reticulum ubiquitin ligase complex, and the p53, and mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways. CONCLUSION: The panel of three-miRNAs (miRNA-7706, miRNA-877-3p, and miRNA-128-3p) may be a useful noninvasive diagnostic biomarker of IHCP. AJTR
OBJECTIVES: Intrahepatic cholestasis of pregnancy (IHCP) causes itching, preterm birth, and stillbirth. However, there is no accurate diagnostic method for IHCP. Currently, circulating microRNAs (miRNAs) have become candidate biomarkers for the diagnosis of multiple diseases. Here, we investigated the diagnostic value of miRNAs in IHCP and aimed to predict the molecular mechanism of IHCP pathogenesis. METHODS: We analyzed differentially expressed miRNAs in both women with IHCP and normal pregnant women. The selected candidate miRNAs were validated in 46 IHCP cases and 46 normal pregnant subjects, and we constructed receiver operator characteristic curves of miRNAs. Pearson correlations between levels of total bile acid (TBA) and differentially expressed miRNAs were also calculated. In addition, we clustered functionally significant biological pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS: The expression levels of 13 miRNAs were remarkably upregulated while the other 35 miRNAs were significantly downregulated, in women with IHCP (P≤0.05) when compared with healthy pregnant women. The areas under the curves of miRNA-7706, miRNA-877-3p, and miRNA-128-3p were higher than 0.90, indicating more reliable diagnosis of IHCP. The Pearson analysis showed that the levels of these miRNAs were positively correlated to TBA level. Additionally, the results of bioinformatics analysis revealed that the differentially expressed miRNAs mainly influenced fatty acid biosynthesis, the endoplasmic reticulum ubiquitin ligase complex, and the p53, and mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways. CONCLUSION: The panel of three-miRNAs (miRNA-7706, miRNA-877-3p, and miRNA-128-3p) may be a useful noninvasive diagnostic biomarker of IHCP. AJTR
Authors: Casey S Yule; Denisse S Holcomb; Alexandria C Kraus; Charles E L Brown; Donald D McIntire; David B Nelson Journal: Am J Perinatol Date: 2020-09-24 Impact factor: 1.862
Authors: William M Hague; Leonie Callaway; Jennifer Chambers; Lucy Chappell; Suzette Coat; Jiska de Haan-Jebbink; Marloes Dekker; Peter Dixon; Jodie Dodd; Maria Fuller; Sanne Gordijn; Dorothy Graham; Oskari Heikinheimo; Annemarie Hennessy; Risto Kaaja; Teck Yee Khong; Laura Lampio; Jennie Louise; Angela Makris; Corey Markus; Hanns-Ulrich Marschall; Philippa Middleton; Ben W Mol; Jonathan Morris; John P Newnham; Caroline Ovadia; Michael Peek; Antonia Shand; Michael Stark; Jim Thornton; Susanna Timonen; Susan Walker; David Warrilow; Catherine Williamson Journal: BMC Pregnancy Childbirth Date: 2021-01-12 Impact factor: 3.007