The Serum microRNA Profile of Intrahepatic Cholestasis of Pregnancy: Identification of Novel Noninvasive Biomarkers

Abstract

Background/aims: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease that significantly increases the risk of fetal complications. Here, we measured serum miRNA levels in ICP patients to identify candidate biomarkers for ICP.

Methods: We used the Agilent miRNA array followed by reverse transcription-polymerase chain reaction assays to identify and validate the serum miRNA profiles of 40 pregnant women with ICP and 40 healthy pregnant controls. We used bioinformatics to identify metabolic processes related to differentially expressed miRNAs.

Results: The expression levels of three miRNAs (miR-371a- 5p, miR-6865-5p, and miR-1182) were significantly increased in ICP patients compared to controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.771, 0.811, and 0.798, respectively. Multiple logistic regression analysis showed that a combination of the levels of the three miRNAs afforded a greater AUC (0.845), thus more reliably diagnosing ICP. The levels of all three miRNAs were positively associated with that of total bile acids. Furthermore, bioinformatics analysis indicated that the three miRNAs principally affected lipid phosphorylation, apoptosis, and the MAPK signaling pathway.

Conclusion: This preliminary work improves our understanding of serum miRNA changes in pregnant women with ICP. The three miRNAs may serve as novel noninvasive biomarkers of ICP.

Keywords: Intrahepatic cholestasis of pregnancy; MicroRNA; Microarray; Noninvasive biomarker.