Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis.

Screening and identification of six serum microRNAs as novel potential combination biomarkers for pulmonary tuberculosis diagnosis.
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DOI:
10.1371/journal.pone.0081076
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Li JC
Li JC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang X;Guo J;Fan S;Li Y;Wei L;Yang X;Jiang T;Chen Z;Wang C;Liu J;Ping Z;Xu D;Wang J;Li Z;Qiu Y;Li JC

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由于缺乏特异性和诊断性标志物,肺结核的发病率很高,因此很难预防肺结核。我们筛选了差异表达的血清microRNAs(miRNAs)作为诊断肺结核的潜在生物标志物。本研究采用Solexa测序法筛选血清miRNAs作为肺结核诊断的潜在生物标志物。茎环定量逆转录聚合酶链反应(qRT-PCR)测定用于验证差异表达的血清miRNAs。分别采用受试者工作特征(ROC)曲线和logistic回归模型分析单个miRNA和组合miRNA诊断的敏感性和特异性。利用预测的靶基因,我们构建了肺结核相关基因和miRNA的调控网络。Solexa测序数据显示,与健康对照相比,肺结核患者中有91种血清miRNA差异表达。经qRT-PCR证实,6种血清miRNAs(hsa-miR-378、hsa-miR-483- 5 p、hsa-miR-22、hsa-miR-29 c、hsa-miR-101和hsa-miR-320 b)在肺结核患者、健康对照组(P<0.001)和鉴别诊断组(包括肺炎、肺癌和慢性阻塞性肺疾病患者)之间差异有统计学意义(P<0.05)。Logistic回归分析显示,6种miRNAs联合检测诊断结核病的敏感性和特异性分别为95.0%和91.8%。miRNAs-基因调控网络揭示了几种miRNAs可能调控免疫途径中的一些靶基因,参与肺结核的发病机制。我们的研究表明,六种血清miRNAs的组合具有很大的潜力,可以作为肺结核的非侵入性生物标志物。
It is very difficult to prevent pulmonary tuberculosis (TB) due to the lack of specific and diagnostic markers, which could lead to a high incidence of pulmonary TB. We screened the differentially expressed serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of pulmonary TB. In this study, serum miRNAs were screened using the Solexa sequencing method as the potential biomarkers for the diagnosis of pulmonary TB. The stem-loop quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was used to verify differentially expressed serum miRNAs. The receiver operating characteristic (ROC) curve and logistic regression model were used to analyze the sensitivity and specificity of the single miRNA and a combination of miRNAs for diagnosis, respectively. Using the predicted target genes, we constructed the regulatory networks of miRNAs and genes that were related to pulmonary TB. The Solexa sequencing data showed that 91 serum miRNAs were differentially expressed in pulmonary TB patients, compared to healthy controls. Following qRT-PCR confirmation, six serum miRNAs (hsa-miR-378, hsa-miR-483-5p, hsa-miR-22, hsa-miR-29c, hsa-miR-101 and hsa-miR-320b) showed significant difference among pulmonary TB patients, healthy controls (P<0.001) and differential diagnosis groups (including patients with pneumonia, lung cancer and chronic obstructive pulmonary disease) (P<0.05). The logistic regression analysis of a combination of six serum miRNAs revealed that the sensitivity and the specificity of TB diagnosis were 95.0% and 91.8% respectively. The miRNAs-gene regulatory networks revealed that several miRNAs may regulate some target genes involved in immune pathways and participate in the pathogenesis of pulmonary TB. Our study suggests that a combination of six serum miRNAs have great potential to serve as non-invasive biomarkers of pulmonary TB.
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发表时间: 2008-09-05
期刊: PloS one
影响因子: 3.7
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