Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma
Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma
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DOI：
10.1093/neuonc/nor169
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发表时间：
2012-01-01
期刊：
影响因子：
15.9
通讯作者：
Schroers, Roland
中科院分区：
文献类型：
--
作者：
Baraniskin, Alexander;Kuhnhenn, Jan;Schroers, Roland
恶性胶质瘤是颅内最常见和最致命的原发性肿瘤。到目前为止，还没有确定用于神经胶质瘤检测和风险分层的可靠生物标志物。最近，我们证明了在原发性CNS淋巴瘤患者的脑脊液（CSF）样本中存在显著水平的微小RNA（miRNA）。由于miRNA参与了胶质瘤的发生发展过程，因此脑脊液中的miRNA可能成为胶质瘤微创诊断的独特生物标志物。这项初步研究的目的是鉴定胶质瘤患者CSF样本中差异表达的microRNA作为潜在的新型胶质瘤生物标志物。通过使用通过逆转录酶聚合酶链反应（qRT-PCR）进行miRNA定量的候选方法，鉴定了来自胶质瘤患者的CSF样品中具有显著水平的miRNA。miR-15 b和miR-21在神经胶质瘤患者的CSF样本中与患有各种神经系统疾病的对照受试者（包括患有原发性CNS淋巴瘤和癌性脑转移的患者）相比差异表达。miR-15 b水平的受试者操作特征分析显示，在区分患有胶质瘤的患者和没有胶质瘤的患者中，曲线下面积为0.96。此外，在联合表达分析中纳入miR-15 b和miR-21导致诊断准确性增加，敏感性为90%，特异性为100%，可将胶质瘤患者与对照受试者和原发性CNS淋巴瘤患者区分开来。总之，该初步研究的结果表明，miR-15 b和miR-21是胶质瘤的标志物，可以通过qRT-PCR在CSF中进行评估。因此，CSF中的miRNAs具有作为用于检测神经胶质瘤的新型生物标志物的潜力。
Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma. The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers. With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver-operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma. In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.