Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

被引:50
作者
Kopkova, Alena [1 ]
Sana, Jiri [1 ,2 ]
Machackova, Tana [1 ]
Vecera, Marek [1 ]
Radova, Lenka [1 ]
Trachtova, Karolina [1 ]
Vybihal, Vaclav [3 ,4 ]
Smrcka, Martin [3 ,4 ]
Kazda, Tomas [4 ,5 ]
Slaby, Ondrej [1 ,2 ]
Fadrus, Pavel [3 ,4 ]
机构
[1] Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
[2] Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech Republic
[3] Univ Hosp Brno, Dept Neurosurg, Brno 62500, Czech Republic
[4] Masaryk Univ, Fac Med, Brno 62500, Czech Republic
[5] Masaryk Univ, Fac Med, Masaryk Mem Canc Inst, Dept Radiat Oncol, Brno 65653, Czech Republic
关键词
glioblastoma; meningioma; brain metastases; microRNA; cerebrospinal fluid; MALIGNANT PROGRESSION; GLIOBLASTOMA; IDENTIFICATION; EPIDEMIOLOGY; MENINGIOMA; EXPRESSION; GLIOMA; CSF;
D O I
10.3390/cancers11101546
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:12
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