Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Neuro Oncol. 2012 Jun;14(6):689-700. doi: 10.1093/neuonc/nos074. Epub 2012 Apr 4.
An accurate, nonsurgical diagnostic test for brain tumors is currently unavailable, and the methods of monitoring disease progression are not fully reliable. MicroRNA profiling of biological fluids has recently emerged as a diagnostic tool for several pathologic conditions. Here we tested whether microRNA profiling of cerebrospinal fluid (CSF) enables detection of glioblastoma, discrimination between glioblastoma and metastatic brain tumors, and reflects disease activity. We determined CSF levels of several cancer-associated microRNAs for 118 patients diagnosed with different types of brain cancers and nonneoplastic neuropathologies by quantitative reverse transcription PCR analysis. The levels of miR-10b and miR-21 are found significantly increased in the CSF of patients with glioblastoma and brain metastasis of breast and lung cancer, compared with tumors in remission and a variety of nonneoplastic conditions. Members of the miR-200 family are highly elevated in the CSF of patients with brain metastases but not with any other pathologic conditions, allowing discrimination between glioblastoma and metastatic brain tumors. Quantification of as few as 7 microRNAs in CSF enables differential recognition of glioblastoma and metastatic brain cancer using computational machine learning tools (Support Vector Machine) with high accuracy (91%-99%) on a test set of samples. Furthermore, we show that disease activity and treatment response can be monitored by longitudinal microRNA profiles in the CSF of glioblastoma and non-small cell lung carcinoma patients. This study demonstrates that microRNA-based detection of brain malignancies can be reliably performed and that microRNAs in CSF can serve as biomarkers of treatment response in brain cancers.
目前，脑肿瘤尚无准确的非手术诊断测试，而监测疾病进展的方法也不完全可靠。生物体液的 microRNA 分析最近已成为几种病理情况的诊断工具。在这里，我们测试了脑脊液（CSF）中的 microRNA 分析是否能够检测出神经胶质瘤，区分神经胶质瘤和转移性脑肿瘤，并反映疾病活动。我们通过定量逆转录 PCR 分析，对 118 名被诊断为不同类型脑癌和非神经病理的患者的 CSF 进行了几种癌症相关 microRNA 的检测。与缓解期肿瘤和多种非肿瘤性疾病相比，miR-10b 和 miR-21 在神经胶质瘤和乳腺癌、肺癌脑转移患者的 CSF 中水平明显升高。miR-200 家族成员在脑转移患者的 CSF 中高度升高，但在其他任何病理情况下均未升高，从而可以区分神经胶质瘤和转移性脑肿瘤。使用计算机器学习工具（支持向量机）对样本测试集进行高精度（91%-99%）的区分，仅需对 CSF 中 7 个 microRNA 进行定量，即可识别神经胶质瘤和转移性脑癌。此外，我们还表明，脑胶质瘤和非小细胞肺癌患者的 CSF 中 microRNA 的纵向分析可以监测疾病活动和治疗反应。本研究表明，基于 microRNA 的脑恶性肿瘤检测可以可靠地进行，CSF 中的 microRNA 可以作为脑癌治疗反应的生物标志物。
