Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system
Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system
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DOI：
10.1182/blood-2010-09-308684
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发表时间：
2011-03-17
期刊：
影响因子：
20.3
通讯作者：
Schroers, Roland
中科院分区：
文献类型：
--
作者：
Baraniskin, Alexander;Kuhnhenn, Jan;Schroers, Roland
原发性中枢神经系统淋巴瘤（PCNSL）的诊断依赖于脑活检的组织病理学，因为脑脊液（CSF）中的疾病标志物尚未获得足够的诊断准确性。microRNA（miRNAs）是在许多疾病类型（包括癌症）中失调的调节RNA分子。最近，miRNAs显示出作为癌症诊断标志物的前景。在这项研究中，我们证明了miRNA存在于PCNSL患者的CSF中。通过候选方法和通过逆转录聚合酶链反应的miRNA定量，鉴定了PCNSL患者CSF中具有显著水平的miRNA。从患有PCNSL的患者和患有炎性CNS病症和其他神经病症的对照收集的CSF中的miR-21、miR-19和miR-92 a水平表明该方法的显著诊断价值。受试者操作特征分析显示，区分PCNSL和对照组的miR-21、miR-19和miR-92 a CSF水平的曲线下面积分别为0.94、0.98和0.97。更重要的是，联合miRNA分析提高了诊断准确性，灵敏度为95.7%，特异性为96.7%。我们还证明了miRNA在CSF中的显著稳定性。总之，CSF miRNAs是潜在的有用的工具，作为新的非侵入性生物标志物，用于诊断PCNSL。（血。2011; 117（11）：3140-3146）
The diagnosis of primary central nervous system lymphoma (PCNSL) depends on histopathology of brain biopsies, because disease markers in the cerebrospinal fluid (CSF) with sufficient diagnostic accuracy are not available yet. MicroRNAs (miRNAs) are regulatory RNA molecules that are deregulated in many disease types, including cancer. Recently, miRNAs have shown promise as markers for cancer diagnosis. In this study, we demonstrate that miRNAs are present in the CSF of patients with PCNSL. With a candidate approach and miRNA quantification by reverse transcription polymerase chain reaction, miRNAs with significant levels in the CSF of patients with PCNSL were identified. MiR-21, miR-19, and miR-92a levels in CSF collected from patients with PCNSL and from controls with inflammatory CNS disorders and other neurologic disorders indicated a significant diagnostic value of this method. Receiver-operating characteristic analyses showed area under the curves of 0.94, 0.98, and 0.97, respectively, for miR-21, miR-19, and miR-92a CSF levels in discriminating PCNSL from controls. More importantly, combined miRNA analyses resulted in an increased diagnostic accuracy with 95.7% sensitivity and 96.7% specificity. We also demonstrated a remarkable stability of miRNAs in the CSF. In conclusion, CSF miRNAs are potentially useful tools as novel noninvasive biomarker for the diagnosis of PCNSL. (Blood. 2011; 117(11):3140-3146)