Gao Zhiying, Zhou Likun, Bai Jing, Ding Meng, Liu Deshui, Zheng Shaohai, Li Yuewen, Li Xiulan, Wang Xiaojuan, Jin Ming, Shangting Huizi, Qiu Changchun, Wang Cheng, Zhang Xiaojie, Zhang Chenyu, Chen Xi
The Institute of Medicine, Qiqihar Medical University, Qiqihar, China.
State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
Ann Transl Med. 2021 Apr;9(8):638. doi: 10.21037/atm-20-7354.
Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections and can lead to adverse pregnancy outcomes (APOs). 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 for HCMV-encoded miRNAs in maternal plasma as an indicator for APOs has never been evaluated.
Expression profiles of 22 HCMV-encoded miRNAs were first measured in plasma samples from 20 pregnant women with APOs and 28 normal controls using quantitative reverse-transcription polymerase chain reaction. Next, markedly changed miRNAs were validated in another independent validation set consisting of 20 pregnant women with APOs and 27 control subjects. Markedly changed miRNAs were further assessed in the placenta tissues. 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 training and validation sets. Diagnostic value and risk factors were compared between APO cohorts and normal controls.
Analysis of the training and validation data sets revealed that plasma concentrations of hcmv-miR-UL148D, hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were significantly increased in pregnant women with APOs compared with normal controls. Hcmv-miR-US25-1-5p presented the largest area under the receiver-operating characteristic (ROC) curve (AUC) (0.735; 95% CI, 0.635-0.836), with a sensitivity of 68% and specificity of 71%. Furthermore, plasma levels of hcmv-miR-US25-1-5p and hcmv-miR-US5-1 correlated positively with APOs (P=0.029 and 0.035, respectively). Hcmv-miR-US25-1-5p in the placenta tissues were dramatically increased in APOs, and correlated with plasma hcmv-miR-US25-1-5p. Nevertheless, neither the concentration of HCMV DNA in PBLs nor the positivity rates of anti-HCMV IgM and anti-HCMV IgG in plasma showed a statistically significant correlation with APOs.
We identified a unique signature of HCMV-encoded miRNAs in pregnant women with APOs that may be useful as a potential noninvasive biomarker for predicting and monitoring APOs during HCMV infection.
人巨细胞病毒（HCMV）是先天性感染最常见的病因，可导致不良妊娠结局（APO）。HCMV编码多种微小RNA（miRNA），据报道这些miRNA部分与宿主免疫反应、细胞周期调控、病毒复制及病毒潜伏有关，且可在人血浆中检测到。然而，HCMV编码的miRNA在孕妇血浆中作为APO指标的相关性从未被评估过。
首先使用定量逆转录聚合酶链反应检测20例有APO的孕妇和28例正常对照血浆样本中22种HCMV编码miRNA的表达谱。接下来，在另一个由20例有APO的孕妇和27例对照受试者组成的独立验证集中验证显著变化的miRNA。在胎盘组织中进一步评估显著变化的miRNA。在训练集和验证集中还检测了外周血白细胞（PBL）中的HCMV DNA以及血浆中的抗HCMV免疫球蛋白M（IgM）和抗HCMV免疫球蛋白G（IgG）。比较APO队列和正常对照之间的诊断价值和危险因素。
对训练集和验证数据集的分析显示，与正常对照相比，有APO的孕妇血浆中hcmv-miR-UL148D、hcmv-miR-US25-1-5p和hcmv-miR-US5-1的浓度显著升高。hcmv-miR-US25-1-5p在受试者工作特征（ROC）曲线下面积最大（AUC）（0.735；95%CI，0.635 - 0.836），敏感性为68%，特异性为71%。此外，hcmv-miR-US25-1-5p和hcmv-miR-US5-1的血浆水平与APO呈正相关（分别为P = 0.029和0.035）。APO患者胎盘组织中的hcmv-miR-US25-1-5p显著增加，并与血浆hcmv-miR-US25-1-5p相关。然而，PBL中HCMV DNA的浓度以及血浆中抗HCMV IgM和抗HCMV IgG的阳性率与APO均无统计学显著相关性。
我们在有APO的孕妇中鉴定出HCMV编码miRNA的独特特征谱，这可能作为预测和监测HCMV感染期间APO的潜在非侵入性生物标志物。
