Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, 400038, China.
Virol J. 2018 Apr 23;15(1):73. doi: 10.1186/s12985-018-0982-y.
To investigate the predictive capability of microRNAs (miRNAs) prior treatment for HBsAg clearance in chronic hepatitis B (CHB) treated with pegylated interferon α-2a (PEG-IFNα-2a).
The treatment effect was determined by HBsAg clearance and subjects were classified into HBsAg clearance group and non HBsAg clearance group. Differential miRNAs expression in peripheral blood mononuclear cells (PBMC) was screened using microarrays in an identification cohort (n = 20) and validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in a confirmation cohort (n = 47). Receiver operating characteristic curve (ROC), logistic regression and gene ontology (GO)/Pathway analyses were used to evaluate the predictive capability of selected miRNAs for HBsAg clearance and determine their mechanistic roles.
Twenty-seven subjects (40.3%) acquired HBsAg clearance, ten in the identification cohort and seventeen in the confirmation cohort. Four miRNAs out of twelve (miR-3960, miR-126-3p, miR-335-5p, miR-23a-3p) were verified to be differential expressed by qRT-PCR in the confirmation cohort. Their expression patterns were consistent with the microarray results. Their levels were lower in the response group compared with the nonresponse group (p < 0.05). The areas under curve (AUC) were 0.8333 (p = 0.001), 0.751 (p = 0.01), 0.7294 (p = 0.013), 0.6275 (p = 0.094) and positive predict values (PPV) were 84.62, 60.00, 70.00, 28.57% for miR-3960, miR-126-3p, miR-335-5p, and miR-23a-3p respectively. The AUC and PPV of the combination of miR-3960 and miR-126-3p were 0.8529 and 92.31%, which were better than using miR-3960 alone, but the differences were not statistically significance (p > 0.05).
We identified differential expressed miRNAs between response and nonresponse groups of PEG-IFNα-2a treatment and demonstrated that miR-3960 was the optimal predictor for HBsAg clearance compared with other miRNAs, but it requires to be further comfired in larger cohort studies.
ChiCTR ChiCTR-ROC-16008735, registered retrospectively on 28 June, 2016.
为了研究聚乙二醇干扰素α-2a（PEG-IFNα-2a）治疗慢性乙型肝炎（CHB）患者中，miRNAs 对 HBsAg 清除的预测能力。
通过 HBsAg 清除率来确定治疗效果，并将患者分为 HBsAg 清除组和非 HBsAg 清除组。采用微阵列技术在鉴定队列（n=20）中筛选外周血单个核细胞（PBMC）中的差异表达 miRNA，并在验证队列（n=47）中采用定量逆转录聚合酶链反应（qRT-PCR）进行验证。采用受试者工作特征曲线（ROC）、逻辑回归和基因本体（GO）/通路分析来评估选定 miRNA 对 HBsAg 清除的预测能力，并确定其作用机制。
27 例（40.3%）患者获得 HBsAg 清除，其中 10 例在鉴定队列中，17 例在验证队列中。通过 qRT-PCR 验证了 12 个 miRNA 中有 4 个（miR-3960、miR-126-3p、miR-335-5p、miR-23a-3p）在验证队列中差异表达。它们的表达模式与微阵列结果一致。与非应答组相比，应答组的水平较低（p<0.05）。曲线下面积（AUC）分别为 0.8333（p=0.001）、0.751（p=0.01）、0.7294（p=0.013）、0.6275（p=0.094），miR-3960、miR-126-3p、miR-335-5p 和 miR-23a-3p 的阳性预测值（PPV）分别为 84.62%、60.00%、70.00%和 28.57%。miR-3960 和 miR-126-3p 的组合 AUC 和 PPV 分别为 0.8529%和 92.31%，优于单独使用 miR-3960，但差异无统计学意义（p>0.05）。
我们鉴定了 PEG-IFNα-2a 治疗应答和非应答组之间差异表达的 miRNAs，并表明 miR-3960 是预测 HBsAg 清除的最佳指标，优于其他 miRNAs，但需要在更大的队列研究中进一步证实。
ChiCTR ChiCTR-ROC-16008735，2016 年 6 月 28 日回顾性注册。
