title: Prognostic role of circulating exosomal miRNAs in multiple myeloma.
abstract: Exosomes, secreted by several cell types, including cancer cells, can be isolated from the peripheral blood and have been shown to be powerful markers of disease progression in cancer. In this study, we examined the prognostic significance of circulating exosomal microRNAs (miRNAs) in multiple myeloma (MM). A cohort of 156 patients with newly diagnosed MM, uniformly treated and followed, was studied. Circulating exosomal miRNAs were isolated and used to perform a small RNA sequencing analysis on 10 samples and a quantitative reverse transcription polymerase chain reaction (qRT-PCR) array on 156 samples. We studied the relationship between miRNA levels and patient outcomes, including progression-free survival (PFS) and overall survival (OS). We identified miRNAs as the most predominant small RNAs present in exosomes isolated from the serum of patients with MM and healthy controls by small RNA sequencing of circulating exosomes. We then analyzed exosomes isolated from serum samples of 156 patients using a qRT-PCR array for 22 miRNAs. Two of these miRNAs, let-7b and miR-18a, were significantly associated with both PFS and OS in the univariate analysis and were still statistically significant after adjusting for the International Staging System and adverse cytogenetics in the multivariate analysis. Our findings support the use of circulating exosomal miRNAs to improve the identification of patients with newly diagnosed MM with poor outcomes. The results require further validation in other independent prospective MM cohorts.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.|Department of Hematology, University Hospital Center of Lille, Lille, France.|INSERM Unité Mixte de Recherche (UMR)-S1172, Lille 2 University, Lille, France.
authors.forename: Salomon
authors.initials: S
authors.lastname: Manier
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.|Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Laboratory for Genomics in Myeloma, INSERM Unité 1037, Toulouse University Hospital, Toulouse, France.
authors.forename: Hervé
authors.identifier: 0000-0002-3050-0140
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Jiantao
authors.identifier: 0000-0002-0039-8800
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Federico
authors.initials: F
authors.lastname: Campigotto
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Karma Z
authors.initials: KZ
authors.lastname: Salem
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Daisy
authors.identifier: 0000-0002-4633-4570
authors.initials: D
authors.lastname: Huynh
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Siobhan V
authors.initials: SV
authors.lastname: Glavey
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Rivotto
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.|Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Coordinamento e Progettazione Ricerca Clinica, Compressible-Fluid Dynamics for Renewable Energy Applications (CREA) Laboratory, Brescia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sacco
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.|Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Coordinamento e Progettazione Ricerca Clinica, Compressible-Fluid Dynamics for Renewable Energy Applications (CREA) Laboratory, Brescia, Italy.
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Juliette
authors.initials: J
authors.lastname: Bouyssou
authors.affiliation: Center for Cancer Research Nantes-Angers, UMR-892 INSERM-6299 Centre National de la Recherche Scientifique, and.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Minvielle
authors.affiliation: Department of Hematology, University Hospital Center of Nantes, Nantes, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Department of Hematology, University Hospital Center of Lille, Lille, France.
authors.forename: Thierry
authors.identifier: 0000-0001-7705-8460
authors.initials: T
authors.lastname: Facon
authors.affiliation: Department of Hematology, University Hospital Center of Poitiers, Poitiers, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Laboratory for Genomics in Myeloma, INSERM Unité 1037, Toulouse University Hospital, Toulouse, France.
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.affiliation: Laboratory for Genomics in Myeloma, INSERM Unité 1037, Toulouse University Hospital, Toulouse, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Trippa
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D000069286:Bortezomib / Q000627:therapeutic use; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000627:therapeutic use; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007621:Karyotyping; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D000069286:Bortezomib; D003907:Dexamethasone; D008558:Melphalan