title: miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications.
abstract: Uveal melanoma (UM) represents approximately 5-6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available, accurate diagnosis is not always easily feasible because of potential accidents (e.g., intraocular hemorrhage). Based on the assumption that the profile of circulating miRNAs is often altered in human cancers, we verified whether UM patients showed different vitreous humor (VH) or serum miRNA profiles with respect to healthy controls. By using TaqMan Low Density Arrays, we analyzed 754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy donors: our data demonstrated that the UM VH profile was unique and only partially overlapping with that from serum of the same patients. Whereas, 90% of miRNAs were shared between VH and vitreal exosomes, and their alterations in UM were statistically overlapped with those of VH and vitreal exosomes, suggesting that VH alterations could result from exosomal dysregulation. We report 32 miRNAs differentially expressed in UM patients in at least 2 different types of samples analyzed. We validated these data on an independent cohort of 12 UM patients. Most alterations were common to VH and vitreal exosomes (e.g., upregulation of miR-21,-34 a,-146a). Interestingly, miR-146a was upregulated in the serum of UM patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or serum alterations in UM could be the consequence of disregulation arising from tumoral cells. Our findings suggest the possibility to detect in VH and serum of UM patients "diagnostic" miRNAs released by the affected eye: based on this, miR-146a could be considered a potential circulating marker of UM.
authors.affiliation: a Molecular, Genome and Complex Systems BioMedicine Unit; Department of Biomedical Sciences and Biotechnology; University of Catania ; Catania , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ragusa
authors.affiliation: a Molecular, Genome and Complex Systems BioMedicine Unit; Department of Biomedical Sciences and Biotechnology; University of Catania ; Catania , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Barbagallo
authors.affiliation: a Molecular, Genome and Complex Systems BioMedicine Unit; Department of Biomedical Sciences and Biotechnology; University of Catania ; Catania , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Statello
authors.affiliation: b Department G.F. Ingrassia, Section of Anatomic Pathology ; University of Catania ; Catania ; Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Caltabiano
authors.affiliation: c Department of Ophthalmology ; University of Catania ; Catania , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Russo
authors.affiliation: b Department G.F. Ingrassia, Section of Anatomic Pathology ; University of Catania ; Catania ; Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Puzzo
authors.affiliation: c Department of Ophthalmology ; University of Catania ; Catania , Italy.
authors.forename: Teresio
authors.initials: T
authors.lastname: Avitabile
authors.affiliation: c Department of Ophthalmology ; University of Catania ; Catania , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Longo
authors.affiliation: c Department of Ophthalmology ; University of Catania ; Catania , Italy.
authors.forename: Mario D
authors.initials: MD
authors.lastname: Toro
authors.affiliation: a Molecular, Genome and Complex Systems BioMedicine Unit; Department of Biomedical Sciences and Biotechnology; University of Catania ; Catania , Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Barbagallo
authors.affiliation: d University of Gothenburg; Department of Rheumatology and Inflammation Research ; Gothenburg , Sweden.
authors.forename: Hadi
authors.initials: H
authors.lastname: Valadi
authors.affiliation: a Molecular, Genome and Complex Systems BioMedicine Unit; Department of Biomedical Sciences and Biotechnology; University of Catania ; Catania , Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Di Pietro
authors.affiliation: a Molecular, Genome and Complex Systems BioMedicine Unit; Department of Biomedical Sciences and Biotechnology; University of Catania ; Catania , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Purrello
authors.affiliation: c Department of Ophthalmology ; University of Catania ; Catania , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Reibaldi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D055354:Exosomes / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D059467:Transcriptome; D014604:Uveal Neoplasms / Q000097:blood* / Q000175:diagnosis; D014822:Vitreous Body / Q000378:metabolism*; D000098943:Uveal Melanoma
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: exosomes, microRNAs, serum, uveal melanoma, vitreous humor