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循环 miR-29c、miR-30c、miR-193a-5p 和 miR-885-5p:HTLV-1 感染诊断的新型潜在生物标志物。

Circulating miR-29c, miR-30c, miR-193a-5p and miR-885-5p: Novel potential biomarkers for HTLV-1 infection diagnosis.

机构信息

Laboratory of Cancer biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.

Laboratory of Cancer biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.

出版信息

Infect Genet Evol. 2019 Oct;74:103938. doi: 10.1016/j.meegid.2019.103938. Epub 2019 Jun 23.

DOI:10.1016/j.meegid.2019.103938
PMID:31242452
Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an oncoretrovirus that infects 5-10 million people worldwide. Currently, different methods are used to test HTLV-1 infection. However, a biomarker that could enable an early and accurate diagnosis of HTLV-1 infection is still lacking. Here, we compared the serum miRNA expression profile in HTLV-1 infected patients versus healthy individuals to identify a potential biomarker for diagnosis of HTLV-1 infection.TaqMan miRNA microarray (TLDA) was carried out to compare the miRNA expression profile in infected versus healthy individuals. Quantitative real-time RT-PCR (qRT-PCR) was applied to validate TLDA results. Receiver-operator characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of the most highly and significantly identified deregulated miRNA(s) as potential biomarker(s). We identified deregulated expression for ten miRNAs with miR-127, miR-136, miR-142-3p, miR-221, and miR-423-5p being down-regulated whilst let-7b, miR-29c, miR-30c, miR-193a-5p, and miR-885-5p being up-regulated in infected individuals. ROC curve analyses showed an AUC (Areas Under the ROC Curve) of 0.875 (95% CI: 0.7819-0.9581; P = .0021), 0.861 (95% CI: 0.7596-0.9754; P = .003), 0.856 (95% CI: 0.689-0.895; P = .011), and 0.849 (95% CI: 0.678-0.855; P = .017) for miR-29c, miR-30c, miR-193a-5p, and miR-885-5p respectively. Combined ROC analyses using these 4 miRNAs showed a greater AUC of 0.907 (95% CI: 0.809-1; P = .000001) indicating a robust diagnostic value of these 4 miRNAs. Our findings highlight serum miR-29c, miR-30c, miR-193a-5p and miR-885-5p as novel potential biomarkers important for HTLV-1 diagnosis.

摘要

人类 T 细胞白血病病毒 1 型(HTLV-1)是一种逆转录病毒,全球有 500 至 1000 万人感染。目前,有多种方法可用于检测 HTLV-1 感染,但仍缺乏一种可用于早期、准确诊断 HTLV-1 感染的生物标志物。在这里,我们比较了 HTLV-1 感染者与健康个体的血清 miRNA 表达谱,以鉴定潜在的 HTLV-1 感染诊断标志物。我们进行了 TaqMan miRNA 微阵列(TLDA),以比较感染个体与健康个体的 miRNA 表达谱。应用实时定量 RT-PCR(qRT-PCR)验证 TLDA 结果。我们进行了Receiver-operator characteristic(ROC)曲线分析,以确定最显著差异的下调或上调 miRNA 作为潜在生物标志物的诊断准确性。我们发现,在感染个体中,miR-127、miR-136、miR-142-3p、miR-221 和 miR-423-5p 下调,而 let-7b、miR-29c、miR-30c、miR-193a-5p 和 miR-885-5p 上调。ROC 曲线分析显示,miR-29c、miR-30c、miR-193a-5p 和 miR-885-5p 的 AUC(ROC 曲线下面积)分别为 0.875(95%CI:0.7819-0.9581;P=0.0021)、0.861(95%CI:0.7596-0.9754;P=0.003)、0.856(95%CI:0.689-0.895;P=0.011)和 0.849(95%CI:0.678-0.855;P=0.017)。使用这 4 个 miRNA 进行联合 ROC 分析显示,AUC 为 0.907(95%CI:0.809-1;P=0.000001),表明这 4 个 miRNA 具有更强的诊断价值。我们的研究结果表明,血清 miR-29c、miR-30c、miR-193a-5p 和 miR-885-5p 可作为 HTLV-1 诊断的潜在新型生物标志物。

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