A cerebrospinal fluid microRNA signature as biomarker for glioblastoma

Johnny C Akers; Wei Hua; Hongying Li; Valya Ramakrishnan; Zixiao Yang; Kai Quan; Wei Zhu; Jie Li; Javier Figueroa; Brian R Hirshman; Brittney Miller; David Piccioni; Florian Ringel; Ricardo Komotar; Karen Messer; Douglas R Galasko; Fred Hochberg; Ying Mao; Bob S Carter; Clark C Chen

doi:10.18632/oncotarget.18332

A cerebrospinal fluid microRNA signature as biomarker for glioblastoma

Oncotarget. 2017 Jun 1;8(40):68769-68779. doi: 10.18632/oncotarget.18332. eCollection 2017 Sep 15.

Authors

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 Mao^{7

8}, Bob S Carter¹, Clark C Chen¹

Affiliations

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.

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.

Keywords: CSF; extracellular vesicle; liquid biopsy.

Abstract

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