miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications

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 assumpt...

Descripción completa

Detalles Bibliográficos
Autores: Ragusa, M. (Marco)|||/items/246b6d9a-212c-4cb2-9b0e-262f72d4afd9, Barbagallo, C. (Cristina)|||/items/8d6cf53e-d7be-4b9e-9d4d-cfbe281e6405, Statello, L. (Luisa)|||/items/bd93ff38-fb37-46bd-9274-65da11af7f0f, Caltabiano, R. (Rosario)|||/items/54e5d64d-c047-498e-b7ba-41f3049ca67b, Russo, A.|||/items/6e8fa13f-97a5-4c34-a15f-40d539bb184a, Puzzo, L. (Lidia)|||/items/9bdc0667-4675-43f1-8fa6-e80170e5831d, Avitabile, T. (Teresio)|||/items/88acefcc-15a6-45bf-9124-1149f95aa669, Longo, A. (Antonio)|||/items/f12ed5e0-0f7c-4c69-a594-17013688888e, Toro, M.D. (Mario D.)|||/items/ded9aadd-b4d6-4913-8f2b-b26dcb111ef4, Barbagallo, D. (Davide)|||/items/1e0ce3cf-058e-4e0f-9085-5ff7f325ebd6, Valadi, H. (Hadi)|||/items/f880a69d-c00a-4515-8e54-d6e537730c79, Di Pietro, C. (Cinzia)|||/items/d6067d86-5317-40a8-bd69-63788773bbdd, Purrello, M. (Michele)|||/items/32d3ee1f-a04f-4d03-88a0-24f52ba7a1d2, Reibaldi, M. (Michele)|||/items/1dd3d07f-4dd8-4afb-b0d8-99a56c540bb3
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/122264
Acceso en línea:https://hdl.handle.net/10171/122264
Access Level:acceso abierto
Palabra clave:exosomes
microRNAs
serum
uveal melanoma
vitreous humor
Descripción
Sumario: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.