Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)
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DOI:
10.1182/blood-2011-06-358382
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发表时间:
2011-11-24
期刊:
影响因子:
20.3
通讯作者:
Odum, Niels
Odum, Niels
中科院分区:
医学1区
文献类型:
--
作者:
Ralfkiaer, Ulrik;Hagedorn, Peter H.;Odum, Niels

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皮肤T细胞淋巴瘤(CTCL)是最常见的原发性皮肤淋巴瘤。然而,由于临床和组织学与良性炎症性皮肤病相似,早期疾病的诊断已被证明是困难的。为了解决microRNA(miRNA)分析是否可以区分CTCL与良性炎症,我们研究了198例CTCL,外周T细胞淋巴瘤(PTL)和良性皮肤病(银屑病和皮炎)患者的miRNA表达水平。使用微阵列,我们表明,最诱导的(miR-326,miR-663 b和miR-711)和抑制的(miR-203和miR-205)miRNA区分CTCL与良性皮肤疾病,在90个样本的训练集和58个盲样的测试集中具有> 90%的准确性。这些miRNAs还在50名PTL和皮肤炎症患者的独立组中以及在银屑病和CTCL的实验性人类异种移植小鼠模型中区分恶性和良性病变。对103例CTCL和良性皮肤病患者的定量(q)RT-PCR分析验证了5种miRNA中4种的差异表达,并证实了先前关于CTCL中miR-155的报道。由miR-155、miR-203和miR-205组成的基于qRT-PCR的分类器以高特异性和灵敏度将CTCL与良性疾病区分开,并且分类准确率为95%,表明miRNA在CTCL中具有高诊断潜力。(血。2011;118(22):5891-5900)
Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL. (Blood. 2011;118(22):5891-5900)