Serum Exosomes MicroRNAs Are Novel Non-Invasive Biomarkers of Intrahepatic Cholestasis of Pregnancy

Abstract

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is closely related to the occurrence of adverse outcomes. Currently, total bile acids (TBAs) are the only diagnostic index for ICP, and its sensitivity and specificity have certain limitations. In this study, we aimed to develop potential biomarkers for the diagnosis of ICP.MethodsSixty pregnant women diagnosed with ICP and 48 healthy pregnant controls were enrolled in this study. We used the Agilent microRNA (miRNA) array followed by quantitative reverse transcriptase polymerase chain reaction assays to identify and validate the serum exosome miRNA profiles in ICP and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed serum exosome miRNAs.ResultsThe expression levels of hsa-miR-4271, hsa-miR-1275, and hsa-miR-6891-5p in maternal serum exosomes were significantly lower in ICP patients compared to controls; the diagnostic accuracy of hsa-miR-4271, hsa-miR-1275, and hsa-miR-6891-5p was evaluated with the area under the receiver operating characteristic curve (AUC) values of 0.861, 0.886, and 0.838, respectively. Multiple logistic regression analysis showed that a combination of the levels of hsa-miR-4271and hsa-miR-1275 afforded a significantly higher AUC (0.982). The non-error rate of a combination of all three exosome miRNAs was the highest (95%), thus more reliable ICP diagnosis. The expression levels of all three exosome miRNAs were negatively associated with TBAs. Furthermore, according to bioinformatics analysis, the three exosome miRNAs were related to lipid metabolism, apoptosis, oxidative stress, and the Mitogen Activated Protein Kinase (MAPK) signaling pathway.ConclusionsThis study may identify the novel non-invasive biomarkers for ICP and provided new insights into the important role of the exosome miRNA regulation in ICP.

The role of noncoding RNA and its diagnostic potential in intrahepatic cholestasis of pregnancy: a research update

“…In another study, the researchers extracted exosomes from the serum of normal pregnant women and those with ICP and observed that t miR-4217, miR-1275, and miR-6891-5p expression in maternal serum exosomes was significantly lower in patients with ICP than in controls. Bioinformatics analysis revealed that the three exosomal miRNAs were primarily associated with the MAPK signaling pathway, which is closely associated with lipid metabolism (Dong et al, 2022). In conclusion, the miRNAs in serum and serum exosomes may act on lipid metabolism and the MAPK and AMPK signaling pathways, thereby inducing ICP onset.…”