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 researchers from Brigham and Women’s Hospital tested whether microRNA profiling of cerebrospinal fluid (CSF) enables detection of glioblastoma, discrimination between glioblastoma and metastatic brain tumors, and reflects disease activity. They 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, the researchers 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.

(A) Classification tree of brain cancer patients based on CSF miRNA biomarkers (miR-10b, -21, and -200). (B and C) Application of SVM with linear kernel to classification of specimens: (B) classification of GBM vs metastatic brain cancer on the basis of Ct levels of 2 miRNAs (miR-200a and miR-125b) in the CSF. (C) Classification of GBM and brain metastasis versus nonneoplastic control cases on the basis of Ct levels of 3 miRNAs (miR-10b, miR-200a, and miR-125b) in the CSF. (D) The relation between miR-10b and miR-21 levels in brain tumors and matching CSF samples collected from the same patients. (E) Relative miR-124a levels were determined in CSF of a randomly selected cohort of control and brain cancer patients by qRT-PCR analysis.

Computational classification of high-grade brain malignancies based on CSF miRNA profiling and the origin of miRNA in CSF

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Reference

Teplyuk et al. (2012) MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol 14(6), 689-700. [abstract]