Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.

Cerebrospinal fluid (CSF) is a body fluid that has many important functions and is in direct contact with the extracellular environment of the central nervous system (CNS). CSF serves as both the communication channel allowing the distribution of various substances among the CNS cells and the storage facility for the waste products these cells release. For these reasons, CSF is a potential source of diagnostic biomarkers of many CNS diseases, including brain tumors. Recent studies have revealed that CSF also contains circulating microRNAs (miRNAs), short non-coding RNAs that have been described as biomarkers in many cancers. However, CSF miRNAs are difficult to detect, which is why researchers face major challenges, including technological difficulties in its detection and its lack of standardization. Therefore, this review aims (i) to highlight the potential of CSF miRNAs as diagnostic, prognostic and predictive biomarkers in brain tumors, and (ii) to summarize technological approaches for detection of CSF miRNAs.

Associated with the pathogenesis of many cancers, including brain tumors, microRNAs (miRNAs) present promising diagnostic biomarkers. These molecules have been also studied in cerebrospinal fluid (CSF), showing great potential as a diagnostic tool in patients with brain tumors. Even though there are some biological and technological factors that could affect the results and their biological and clinical interpretation, miRNA analysis in CSF is not fully standardized. This study aims to compare several RNA extraction and miRNA quantification approaches, including high-throughput technologies and individual miRNA detection methods, thereby contributing to the optimization and standardization of quantification of extracellular miRNAs in CSF. Such knowledge is essential for the potential use of miRNAs as diagnostic biomarkers in brain tumors.