Cited by 266Extracellular vesicles in diseaseMultiple Myeloma Research and TreatmentsMicroRNA in disease regulation

Prognostic role of circulating exosomal miRNAs in multiple myeloma

Open access
Manier, Salomon, Liu, Chia-Jen, Avet-Loiseau, Hervé, Park, Jihye, Shi, Jiantao, Campigotto, Federico, Salem, Karma Z., Huynh, Daisy +12 more·2017·Blood

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.

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Crossref · 10.1182/blood-2016-09-742296

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  • Proteasome inhibitor treatment alters miRNAs.

    “Proteasome inhibitor leads to alteration in not only the proteins but also the miRNAs (12, 13).”

    From miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer (2021) · cites this paper as [12]

    The ‘Exosomal miRNAs and survival in MM’ section says serum was collected before bortezomib-and-dexamethasone therapy and analyzes baseline miRNAs as prognostic markers. The ‘Statistical analysis’ section likewise describes newly diagnosed, untreated patients. Neither passage establishes that proteasome inhibitor treatment alters miRNAs; searches for treatment-related miRNA changes found no such result in our copy. (LLM, conf=0.77)

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Authors
Manier, S., Liu, C.-J., Avet-Loiseau, H., Park, J., Shi, J., Campigotto, F., Salem, K. Z., Huynh, D., Glavey, S. V., Rivotto, B., Sacco, A., Roccaro, A. M., Bouyssou, J., Minvielle, S., Moreau, P., Facon, T., Leleu, X., Weller, E., Trippa, L., & Ghobrial, I. M.
Affiliations
  • Harvard University (US)
  • Laboratory for Genomics in Myeloma, INSERM Unité 1037, Toulouse University Hospital, Toulouse, France;
  • Centre National de la Recherche Scientifique (FR)
  • Centre Hospitalier Universitaire de Nantes (FR)
  • Centre Hospitalier Universitaire de Lille (FR)
  • Centre Hospitalier Universitaire de Poitiers (FR)
  • Inserm (FR)
Corresponding author
  • Manier, Salomon
  • Liu, Chia-Jen
Venue
Blood
Published
2017-04-27
Volume
129
Issue
17
Pages
2429-2436
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2588057136
Cited by
266
References
2
Citations by year
2026: 6 · 2025: 21 · 2024: 21 · 2023: 22 · 2022: 33 · 2021: 56 · 2020: 36 · 2019: 40 · 2018: 23 · 2017: 8
FWCI
11.96
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (R01CA154648)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
multiple myeloma, circulating exosomes, exosomal microRNAs, prognostic factors, let-7b, miR-18a, progression-free survival, overall survival, serum exosomes, newly diagnosed multiple myeloma
MeSH terms
Bortezomib, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Female, Humans, Karyotyping, Male, Melphalan, Middle Aged, Multiple Myeloma, Prognosis, Transplantation, Autologous, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Survival Analysis, Case-Control Studies, Treatment Outcome, Sequence Analysis, RNA, Hematopoietic Stem Cell Transplantation, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Cell Line, Tumor, Exosomes

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