Department of Medicine, Hematology and Oncology, Ruhr-University of Bochum, Germany.
Neuro Oncol. 2012 Jan;14(1):29-33. doi: 10.1093/neuonc/nor169. Epub 2011 Sep 21.
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.
恶性胶质瘤是最常见和最致命的原发性颅内肿瘤。迄今为止，尚未发现用于检测和风险分层的可靠生物标志物。最近，我们证明原发性中枢神经系统淋巴瘤患者的脑脊液（CSF）样本中存在显著水平的 microRNAs（miRNAs）。由于 miRNA 参与了致癌作用，CSF 中的 miRNA 可能成为用于微创诊断胶质瘤的独特生物标志物。本研究的目的是鉴定胶质瘤患者 CSF 样本中差异表达的 microRNAs，作为潜在的新型胶质瘤生物标志物。通过逆转录聚合酶链反应（qRT-PCR）进行 miRNA 定量的候选方法，鉴定出在胶质瘤患者 CSF 样本中具有显著水平的 microRNAs。与患有原发性中枢神经系统淋巴瘤和癌性脑转移等各种神经系统疾病的对照组相比，miR-15b 和 miR-21 在胶质瘤患者的 CSF 样本中表达差异。miR-15b 水平的受试者工作特征分析显示，区分胶质瘤患者和非胶质瘤患者的曲线下面积为 0.96。此外，miR-15b 和 miR-21 的纳入联合表达分析可提高诊断准确性，以 90%的敏感性和 100%的特异性区分胶质瘤患者和对照组及原发性中枢神经系统淋巴瘤患者。总之，这项初步研究的结果表明，miR-15b 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 miRNA 有可能成为检测胶质瘤的新型生物标志物。
