A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies

Abstract

// Alessandra Drusco 1 , Arianna Bottoni 1 , Alessandro Laganà 2 , Mario Acunzo 1 , Matteo Fassan 3 , Luciano Cascione 5, 6 , Anna Antenucci 4 , Prasanthi Kumchala 1 , Caterina Vicentini 7 , Marina P. Gardiman 3 , Hansjuerg Alder 1 , Mariantonia A. Carosi 8 , Mario Ammirati 9 , Stefano Gherardi 10 , Marilena Luscrì 10 , Carmine Carapella 11 , Nicola Zanesi 1 , Carlo M. Croce 1 1 MVIMG, The Ohio State University, Columbus, OH, USA 2 Dept. of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA 3 Dept. of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy 4 UOSD of Clinical pathology, Regina Elena Institute, Rome, Italy 5 Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland 6 IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland 7 ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy 8 Dept. of Pathology, Regina Elena Institute, Rome, Italy 9 Dept. of Neurological Surgery, The Ohio State University, OH, USA 10 Dept. of Anesthesiology, Sandro Pertini Hospital, Rome, Italy 11 Dept. of Neurological Surgery, Regina Elena Institute, Rome, Italy Correspondence to: Carlo M. Croce, e-mail: carlo.croce@osumc.edu Alessandra Drusco, e-mail: adrusco@gmail.com Keywords: microRNA, cerebro-spinal fluid (CSF), brain tumors, biomarkers Received: May 02, 2015      Accepted: May 14, 2015      Published: May 28, 2015 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.