title: A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.
abstract: Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications.
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Drusco
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Arianna
authors.initials: A
authors.lastname: Bottoni
authors.affiliation: Dept. of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laganà
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Acunzo
authors.affiliation: Dept. of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.|IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cascione
authors.affiliation: UOSD of Clinical Pathology, Regina Elena Institute, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Antenucci
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Kumchala
authors.affiliation: ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vicentini
authors.affiliation: Dept. of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Gardiman
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.affiliation: Dept. of Pathology, Regina Elena Institute, Rome, Italy.
authors.forename: Mariantonia A
authors.initials: MA
authors.lastname: Carosi
authors.affiliation: Dept. of Neurological Surgery, The Ohio State University, OH, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Ammirati
authors.affiliation: Dept. of Anesthesiology, Sandro Pertini Hospital, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gherardi
authors.affiliation: Dept. of Anesthesiology, Sandro Pertini Hospital, Rome, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Luscrì
authors.affiliation: Dept. of Neurological Surgery, Regina Elena Institute, Rome, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Carapella
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zanesi
authors.affiliation: MVIMG, The Ohio State University, Columbus, OH, USA.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor; D001706:Biopsy; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000134:cerebrospinal fluid; D006801:Humans; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000378:metabolism; D036103:Nanotechnology / Q000379:methods; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: biomarkers; brain tumors; cerebro-spinal fluid (CSF); microRNA