Plasma-Derived Exosome Proteins as Novel Diagnostic and Prognostic Biomarkers in Neuroblastoma Patients

Author:

Morini Martina1ORCID,Raggi Federica2ORCID,Bartolucci Martina3ORCID,Petretto Andrea3ORCID,Ardito Martina1,Rossi Chiara2,Segalerba Daniela1ORCID,Garaventa Alberto4,Eva Alessandra5,Cangelosi Davide6,Bosco Maria Carla2ORCID

Affiliation:

1. Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy

2. Unit of Autoinflammatory Diseases and Immunodeficiencies, Pediatric Rheumatology Clinic, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy

3. Core Facilities, Clinical Proteomics and Metabolomics, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy

4. Pediatric Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy

5. Scientific Directorate, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy

6. Clinical Bioinfomatics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor during infancy, causing up to 10% of mortality in children; thus, identifying novel early and accurate diagnostic and prognostic biomarkers is mandatory. NB-derived exosomes carry proteins (Exo-prots) reflecting the status of the tumor cell of origin. The purpose of this study was to characterize, for the first time, the Exo-prots specifically expressed in NB patients associated with tumor phenotype and disease stage. We isolated exosomes from plasma specimens of 24 HR-NB patients and 24 low-risk (LR-NB) patients at diagnosis and of 24 age-matched healthy controls (CTRL). Exo-prot expression was measured by liquid chromatography–mass spectrometry. The data are available via ProteomeXchange (PXD042422). The NB patients had a different Exo-prot expression profile compared to the CTRL. The deregulated Exo-prots in the NB specimens acted mainly in the tumor-associated pathways. The HR-NB patients showed a different Exo-prot expression profile compared to the LR-NB patients, with the modulation of proteins involved in cell migration, proliferation and metastasis. NCAM, NCL, LUM and VASP demonstrated a diagnostic value in discriminating the NB patients from the CTRL; meanwhile, MYH9, FN1, CALR, AKAP12 and LTBP1 were able to differentiate between the HR-NB and LR-NB patients with high accuracy. Therefore, Exo-prots contribute to NB tumor development and to the aggressive metastatic NB phenotype.

Funder

Fondazione Umberto Veronesi

Publisher

MDPI AG

Subject

General Medicine

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