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Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826583/ https://www.ncbi.nlm.nih.gov/pubmed/31614872 http://dx.doi.org/10.3390/cancers11101546 |
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author | Kopkova, Alena Sana, Jiri Machackova, Tana Vecera, Marek Radova, Lenka Trachtova, Karolina Vybihal, Vaclav Smrcka, Martin Kazda, Tomas Slaby, Ondrej Fadrus, Pavel |
author_facet | Kopkova, Alena Sana, Jiri Machackova, Tana Vecera, Marek Radova, Lenka Trachtova, Karolina Vybihal, Vaclav Smrcka, Martin Kazda, Tomas Slaby, Ondrej Fadrus, Pavel |
author_sort | Kopkova, Alena |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6826583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68265832019-11-18 Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors Kopkova, Alena Sana, Jiri Machackova, Tana Vecera, Marek Radova, Lenka Trachtova, Karolina Vybihal, Vaclav Smrcka, Martin Kazda, Tomas Slaby, Ondrej Fadrus, Pavel Cancers (Basel) Article 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. MDPI 2019-10-12 /pmc/articles/PMC6826583/ /pubmed/31614872 http://dx.doi.org/10.3390/cancers11101546 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kopkova, Alena Sana, Jiri Machackova, Tana Vecera, Marek Radova, Lenka Trachtova, Karolina Vybihal, Vaclav Smrcka, Martin Kazda, Tomas Slaby, Ondrej Fadrus, Pavel Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors |
title | Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors |
title_full | Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors |
title_fullStr | Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors |
title_full_unstemmed | Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors |
title_short | Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors |
title_sort | cerebrospinal fluid microrna signatures as diagnostic biomarkers in brain tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826583/ https://www.ncbi.nlm.nih.gov/pubmed/31614872 http://dx.doi.org/10.3390/cancers11101546 |
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