A cerebrospinal fluid microRNA signature as biomarker for glioblastoma
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Johnny C. Akers1,*, Wei Hua2,*, Hongying Li3,*, Valya Ramakrishnan1, Zixiao Yang2, Kai Quan2, Wei Zhu2, Jie Li1, Javier Figueroa1, Brian R. Hirshman1, Brittney Miller1, David Piccioni4, Florian Ringel5, Ricardo Komotar6, Karen Messer3, Douglas R. Galasko7, Fred Hochberg1, Ying Mao7,8,**, Bob S. Carter1,** and Clark C. Chen1,**
1 Center for Theoretical and Applied Neuro-Oncology, University of California, San Diego, CA, USA
2 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
3 Biostatistics Department, Moores Cancer Center, UC San Diego Health System, La Jolla, CA, USA
4 Department of Neurosurgery, Moores Cancer Center, UC San Diego Health System, La Jolla, CA, USA
5 Department of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
6 Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
7 Department of Neurosciences, University of California, San Diego, CA, USA
8 State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China
* These authors shared responsibility as first authors
** These authors shared responsibility as senior authors
Clark C. Chen, email:
Keywords: extracellular vesicle, CSF, liquid biopsy
Received: April 12, 2017 Accepted: May 19, 2017 Published: June 01, 2017
Purpose: To develop a cerebrospinal fluid (CSF) miRNA diagnostic biomarker for glioblastoma.
Experimental Design: Glioblastoma tissue and matched CSF from the same patient (obtained prior to tumor manipulation) were profiled by TaqMan OpenArray® Human MicroRNA Panel. CSF miRNA profiles from glioblastoma patients and controls were created from three discovery cohorts and confirmed in two validation cohorts.
Results: miRNA profiles from clinical CSF correlated with those found in glioblastoma tissues. Comparison of CSF miRNA profiles between glioblastoma patients and non-brain tumor patients yielded a tumor “signature” consisting of nine miRNAs. The “signature” correlated with glioblastoma tumor volume (p=0.008). When prospectively applied to cisternal CSF, the sensitivity and specificity of the ‘signature’ for glioblastoma detection were 67% and 80%, respectively. For lumbar CSF, the sensitivity and specificity of the signature were 28% and 95%, respectively. Comparable results were obtained from analyses of CSF extracellular vesicles (EVs) and crude CSF.
Conclusion: We report a CSF miRNA signature as a “liquid biopsy” diagnostic platform for glioblastoma.
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