Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients
Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients
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活动性结核病患者外周血单核细胞中环状 RNA 的微阵列表达谱
DOI：
10.1159/000487454
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Li, Jun-Ming
中科院分区：
文献类型：
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作者：
Huang, Zi-Kun;Yao, Fang-Yi;Li, Jun-Ming
背景/目的：环状rna （circRNAs）表达失调被证明与许多疾病有关。在这里，我们旨在检测活动性结核病患者外周血单个核细胞（PBMCs）中的环状rna谱，以鉴定结核病的新生物标志物。方法：采用微阵列法分析3例活动性肺结核患者和3例健康对照者外周血单核细胞中环状rna的表达谱。在40名结核病患者和40名对照组中选择6个circrna进行实时定量PCR （qRT-PCR）验证。构建受试者工作特征（ROC）曲线，评价其在结核病诊断中的价值。选择Hsa_circRNA_001937在一个独立队列中进行进一步评估，该队列包括115名结核病患者、40名肺炎患者、40名COPD患者、40名肺癌患者和90名对照受试者。对20例新诊断结核病患者进行8个月的随访，观察化疗后hsa_circRNA_001937的表达变化。结果：我们发现并证实了许多环状rna在结核病患者中失调。在研究的6种生理circrna中，与健康对照组相比，来自结核病患者的pbmc中hsa_circRNA_001937、hsa_circRNA_009024和hsa_circrna_005086的水平显著升高，hsa_circRNA_102101、hsa_circRNA_104964和hsa_circRNA_104296的水平显著降低。ROC曲线分析显示，hsa_circRNA_001937曲线下面积最大（AUC = 0.873， P<0.001）。Hsa_circRNA_001937在TB患者中与肺炎、COPD和肺癌患者相比显著升高。Hsa_ circRNA_001937与TB严重程度相关（r = 0.4053, P = 0.010），治疗后其表达显著降低。结论：本研究在活跃的TB pbmc中发现了一组失调的环状rna，我们的数据还表明hsa_circRNA_001937可以作为TB的潜在诊断生物标志物。
Background/Aims: Dysregulated expression of circular RNAs (circRNAs) was demonstrated to be implicated in many diseases. Here, we aimed to determine circRNA profile in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients to identify novel biomarkers for TB. Methods: Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3 healthy controls were analyzed by microarray assay. Six circRNAs were selected for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and 40 control subjects. Receiver operating characteristic (ROC) curve was constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was chosen for further evaluation in an independent cohort consisting of 115 TB, 40 pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight-month follow up was performed in 20 newly diagnosed TB patients to investigate the expression change of hsa_circRNA_001937 after chemotherapy. Results: We revealed and confirmed that a number of circRNAs were dysregulated in TB patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937, hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly reduced in PBMCs from TB patients as compared to healthy controls. ROC curve analysis suggested that hsa_circRNA_001937 has the largest area under the curve (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in patients with TB compared with patients with pneumonia, COPD and lung cancer. Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and its expression significantly decreased after treatment. Conclusion: This study identified a set of deregulated circRNAs in active TB PBMCs, our data also suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker of TB.