MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity

Abstract

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.

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

“…Overexpression of miR-10b in otherwise nonmetastatic breast tumors initiated robust invasion and metastasis [8]. miR-10b is a unique miRNA expressed specifically in glioma tumors but not in normal brain cells: neither neural progenitor cells nor mature glia or neurons [9,10]. It has been reported that miR-10b was upregulated in all glioma samples compared with nonneoplastic brain tissues; the expression level of miR-10b was associated with higher-grade glioma and the tumor invasive factors uPAR and RhoC [9].…”

The role of micro-RNA in the regulation of signal pathways in gliomas

“…SVM (support vector machine, один из алгоритмов машинного обучения) показал, что определение уровней экспрессии 7 микро-РНК в ЦСЖ (miR-10b, -21, -141, -200a, -200b, -200c и -125b) позволяет дифференцировать глиобластомы и метастазы мозга с высокой точностью (91-99%) на тестовом наборе данных. Тем не менее, авторы отмечают, что поиск дополнительных микро-РНК-биомаркеров и последующий анализ больших когорт пациентов помогут увеличить точность подхода [130].…”

MicroRNAs Role in the Central Nervous System Development and Abnormalities

“…After miRNAs were first found in CSF [28], several more studies have demonstrated the presence of miRNAs in CSF and their potentials as biomarkers for neurological disease [32][33][34][35]. Further, a study comparing miRNA expression profile from serum and CSF has revealed that miRNA expression pattern is quite consistent among different subjects when miRNAs are from the same type of bio-fluid (serum or CSF).…”