title: Circulating melanoma exosomes as diagnostic and prognosis biomarkers.
abstract: BACKGROUND
  Malignant melanoma is an aggressive cancer with an increasing incidence. Exosomes are actively secreted microvesicles, whose characteristics reflect those of the cell they are originated in. The aim of this study was to identify and evaluate the presence of the melanoma biomarkers MIA, S100B and tyrosinase-related protein 2 (TYRP2) in exosomes and their potential clinical utility.
  
  
  METHODS
  Serum samples were obtained from stage IV melanoma patients, melanoma-free patients and healthy controls. Exosomes were precipitated and TYRP2, MIA and S100B concentrations were quantified in serum, exosomes, and exosome-free serum.
  
  
  RESULTS
  Both MIA and S100B were detected in exosomes and correlated significantly with serum concentrations (S100B: r=0.968; MIA: r=0.799; p<0.001). MIA and S100B concentrations in exosomes were significantly higher in melanoma patients than in healthy controls and disease-free patients. However, TYRP2 concentrations in exosomes did not differ between these three groups. ROC curves analysis rendered AUCs for MIA of 0.883 (p<0.01) and of 0.840 for S100B (p<0.01). Patients with exosome MIA concentration higher than 2.5 μg/L showed shorter median survival related to those with lower level (4 versus 11 months; p<0.05).
  
  
  CONCLUSIONS
  MIA and S100B can be detected in exosomes from melanoma patients and their quantification presents diagnostic and prognostic utility.
authors.affiliation: Laboratory of Biochemistry, University Clinic of Navarra, Spain.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Alegre
authors.affiliation: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Zubiri
authors.affiliation: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Perez-Gracia
authors.affiliation: Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: González-Cao
authors.affiliation: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Soria
authors.affiliation: Department of Medical Oncology, University Clinic of Navarra, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Martín-Algarra
authors.affiliation: Laboratory of Biochemistry, University Clinic of Navarra, Spain. Electronic address: agonzaleh@unav.es.
authors.forename: Alvaro
authors.initials: A
authors.lastname: González
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D045744:Cell Line, Tumor; D055354:Exosomes / Q000737:chemistry*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase
keywords: Exosomes; Melanoma; Melanoma inhibitory activity; S100B