Assessment of HCMV-encoded microRNAs in Plasma as Potential Biomarkers in Pregnant Women with Adverse Pregnancy Outcomes
Background: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections and can lead to adverse pregnancy outcomes (APO). HCMV encodes multiple microRNAs (miRNAs) that have been reported to be partially related to host immune responses, cell cycle regulation, viral replication and viral latency, and can be detected in human plasma. However, the relevance of HCMV-encoded miRNAs in maternal plasma as an indicator for APO has never been evaluated.Methods: The expression
... e expression profiles of 25 HCMV-encoded miRNAs were first measured in plasma samples from 20 pregnant women with APO and 28 normal controls by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) technology. Next, markedly changed miRNAs were validated in another independent validation set consisting of 20 pregnant women with APO and 27 control subjects. HCMV DNA in peripheral blood leukocytes (PBLs) and anti-HCMV immunoglobulin M (IgM) and anti-HCMV immunoglobulin G (IgG) in plasma were also examined in both the training and validation sets. Diagnostic value and risk factors were compared between adverse pregnancy outcome cohorts and normal controls.Results: The analysis of training and validation data sets revealed that plasma concentrations of hcmv-miR-UL148D, hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were obviously increased in pregnant women with APO compared with normal controls. Hcmv-miR-US25-1-5p presented the largest area under the receiver-operating characteristic (ROC) curve (0.735; 95% CI, 0.635–0.836), with a sensitivity of 68% and specificity of 71%. Furthermore, the plasma levels of hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were obviously positively correlated with APO (P = 0.029 and 0.035, respectively). Nevertheless, neither the concentration of HCMV DNA in PBLs nor the positivity rates of anti-HCMV IgM and IgG in plasma showed statistically significant correlation with APO.Conclusion: We identified a unique signature of HCMV-encoded miRNAs in pregnant women with APO, which may be useful as a potential noninvasive biomarker for predicting and monitoring APO during HCMV infection.