A cerebrospinal fluid microRNA signature as biomarker for glioblastoma

// Johnny C. Akers 1,* , Wei Hua 2,* , Hongying Li 3,* , Valya Ramakrishnan 1 , Zixiao Yang 2 , Kai Quan 2 , Wei Zhu 2 , Jie Li 1 , Javier Figueroa 1 , Brian R. Hirshman 1 , Brittney Miller 1 , David Piccioni 4 , Florian Ringel 5 , Ricardo Komotar 6 , Karen Messer 3 , Douglas R. Galasko 7 , Fred Hochberg 1 , Ying Mao 7,8,** , Bob S. Carter 1,** and Clark C. Chen 1,** 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 Correspondence to: Clark C. Chen, email: // Keywords : extracellular vesicle, CSF, liquid biopsy Received : April 12, 2017 Accepted : May 19, 2017 Published : June 01, 2017 Abstract 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.