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A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies
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Alessandra Drusco1, Arianna Bottoni1, Alessandro Laganà2, Mario Acunzo1, Matteo Fassan3, Luciano Cascione5,6, Anna Antenucci4, Prasanthi Kumchala1, Caterina Vicentini7, Marina P. Gardiman3, Hansjuerg Alder1, Mariantonia A. Carosi8, Mario Ammirati9, Stefano Gherardi10, Marilena Luscrì10, Carmine Carapella11, Nicola Zanesi1, Carlo M. Croce1
1MVIMG, The Ohio State University, Columbus, OH, USA
2Dept. of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
3Dept. of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
4UOSD of Clinical pathology, Regina Elena Institute, Rome, Italy
5Lymphoma & Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland
6IOSI Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
7ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy
8Dept. of Pathology, Regina Elena Institute, Rome, Italy
9Dept. of Neurological Surgery, The Ohio State University, OH, USA
10Dept. of Anesthesiology, Sandro Pertini Hospital, Rome, Italy
11Dept. of Neurological Surgery, Regina Elena Institute, Rome, Italy
Carlo M. Croce, e-mail: [email protected]
Alessandra Drusco, e-mail: [email protected]
Keywords: microRNA, cerebro-spinal fluid (CSF), brain tumors, biomarkers
Received: May 02, 2015 Accepted: May 14, 2015 Published: May 28, 2015
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.
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