Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors
被引:50
作者:
Kopkova, Alena
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Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Kopkova, Alena
[1
]
Sana, Jiri
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机构:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Sana, Jiri
[1
,2
]
Machackova, Tana
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机构:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Machackova, Tana
[1
]
Vecera, Marek
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机构:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Vecera, Marek
[1
]
Radova, Lenka
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Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Radova, Lenka
[1
]
Trachtova, Karolina
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机构:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Trachtova, Karolina
[1
]
Vybihal, Vaclav
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机构:
Univ Hosp Brno, Dept Neurosurg, Brno 62500, Czech Republic
Masaryk Univ, Fac Med, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Vybihal, Vaclav
[3
,4
]
Smrcka, Martin
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机构:
Univ Hosp Brno, Dept Neurosurg, Brno 62500, Czech Republic
Masaryk Univ, Fac Med, Brno 62500, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Smrcka, Martin
[3
,4
]
Kazda, Tomas
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机构:
Masaryk Univ, Fac Med, Brno 62500, Czech Republic
Masaryk Univ, Fac Med, Masaryk Mem Canc Inst, Dept Radiat Oncol, Brno 65653, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Kazda, Tomas
[4
,5
]
Slaby, Ondrej
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机构:
Masaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech RepublicMasaryk Univ, Cent European Inst Technol CEITEC, Brno 62500, Czech Republic
Slaby, Ondrej
[1
,2
]
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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
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.
机构:
Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USAOhio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Kyushu Univ, Grad Sch Med Sci, Res Ctr Genet Informat, Div Genome Anal, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Guan, Yanlei
Mizoguchi, Masahiro
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Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Mizoguchi, Masahiro
Yoshimoto, Koji
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Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Yoshimoto, Koji
Hata, Nobuhiro
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Hachisuga Hosp, Dept Neurosurg, Ojinosaka, Munegata 2650, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Hata, Nobuhiro
Shono, Tadahisa
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Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Shono, Tadahisa
Suzuki, Satoshi O.
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Kyushu Univ, Grad Sch Med Sci, Dept Neuropathol, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Suzuki, Satoshi O.
Araki, Yukie
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Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Araki, Yukie
Kuga, Daisuke
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Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Kuga, Daisuke
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Nakamizo, Akira
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Amano, Toshiyuki
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Ma, Xinlong
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Hayashi, Kenshi
Sasaki, Tomio
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
机构:
Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USAOhio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Kyushu Univ, Grad Sch Med Sci, Res Ctr Genet Informat, Div Genome Anal, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Guan, Yanlei
Mizoguchi, Masahiro
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Mizoguchi, Masahiro
Yoshimoto, Koji
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Yoshimoto, Koji
Hata, Nobuhiro
论文数: 0引用数: 0
h-index: 0
机构:
Hachisuga Hosp, Dept Neurosurg, Ojinosaka, Munegata 2650, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Hata, Nobuhiro
Shono, Tadahisa
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Shono, Tadahisa
Suzuki, Satoshi O.
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h-index: 0
机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neuropathol, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Suzuki, Satoshi O.
Araki, Yukie
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Araki, Yukie
Kuga, Daisuke
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Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan
Kuga, Daisuke
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Nakamizo, Akira
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Amano, Toshiyuki
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Ma, Xinlong
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机构:
Hayashi, Kenshi
Sasaki, Tomio
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机构:
Kyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, JapanKyushu Univ, Grad Sch Med Sci, Dept Neurosurg, Higashi Ku, Fukuoka 8128582, Japan