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Prognostic role of circulating exosomal miRNAs in multiple myeloma

Salomon Manier, Chia-Jen Liu, Hervé Avet-Loiseau, Jihye Park, Jiantao Shi, Federico Campigotto, Karma Z. Salem, Daisy Huynh, Siobhan V. Glavey, Bradley Rivotto, Antonio Sacco, Aldo M. Roccaro, Juliette Bouyssou, Stéphane Minvielle, Philippe Moreau, Thierry Facon, Xavier Leleu, Edie Weller, Lorenzo Trippa and Irene M. Ghobrial

Key points

  • Two circulating exosomal microRNAs, namely let-7b and miR-18a, improved survival prediction in patients with multiple myeloma.

  • Circulating exosomal miRNAs enhanced the stratification of patients with high-risk factors.

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 small RNA sequencing analysis on 10 samples and a 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 MM patients 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, namely 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 (ISS), and adverse cytogenetics in the multivariate analysis. Our findings support the use of circulating exosomal miRNAs improves the identification of patients with newly diagnosed MM with poor outcomes. The results require further validation in other independent prospective MM cohorts.

  • Submitted September 28, 2016.
  • Accepted February 7, 2017.