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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/10/1546 |
| _version_ | 1797708566374645760 |
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| author | Alena Kopkova Jiri Sana Tana Machackova Marek Vecera Lenka Radova Karolina Trachtova Vaclav Vybihal Martin Smrcka Tomas Kazda Ondrej Slaby Pavel Fadrus |
| author_facet | Alena Kopkova Jiri Sana Tana Machackova Marek Vecera Lenka Radova Karolina Trachtova Vaclav Vybihal Martin Smrcka Tomas Kazda Ondrej Slaby Pavel Fadrus |
| author_sort | Alena Kopkova |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T06:24:29Z |
| format | Article |
| id | doaj.art-f479605198bd4334885c87e98fad7d1f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:24:29Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f479605198bd4334885c87e98fad7d1f2023-09-03T02:04:50ZengMDPI AGCancers2072-66942019-10-011110154610.3390/cancers11101546cancers11101546Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain TumorsAlena Kopkova0Jiri Sana1Tana Machackova2Marek Vecera3Lenka Radova4Karolina Trachtova5Vaclav Vybihal6Martin Smrcka7Tomas Kazda8Ondrej Slaby9Pavel Fadrus10Central European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicCentral European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicCentral European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicCentral European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicCentral European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicCentral European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicDepartment of Neurosurgery, University Hospital Brno, Brno 625 00, Czech RepublicDepartment of Neurosurgery, University Hospital Brno, Brno 625 00, Czech RepublicFaculty of Medicine, Masaryk University, Brno 625 00, Czech RepublicCentral European Institute of Technology (CEITEC), Masaryk University, Brno 625 00, Czech RepublicDepartment of Neurosurgery, University Hospital Brno, Brno 625 00, Czech RepublicCentral 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.https://www.mdpi.com/2072-6694/11/10/1546glioblastomameningiomabrain metastasesmicrornacerebrospinal fluid |
| spellingShingle | Alena Kopkova Jiri Sana Tana Machackova Marek Vecera Lenka Radova Karolina Trachtova Vaclav Vybihal Martin Smrcka Tomas Kazda Ondrej Slaby Pavel Fadrus Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors Cancers glioblastoma meningioma brain metastases microrna cerebrospinal fluid |
| 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 | glioblastoma meningioma brain metastases microrna cerebrospinal fluid |
| url | https://www.mdpi.com/2072-6694/11/10/1546 |
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