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.

Serum exosomal microRNAs as novel biomarkers for multiple myeloma

“…Previous studies have shown that plasma levels of miRNA are associated with ISS disease stage and PFS in myeloma . The expression levels of miR‐16 and miR‐20a, along with those of let‐7a, let‐7b, let‐7i, miR‐15b, and miR‐20a, were significantly abnormal in myeloma serum, and microRNAs showed different expression in serum from patients with monoclonal immunoglobulin‐related diseases, including monoclonal gammopathy of undetermined significance (MGUS), SMM, and MM . Exosomes, which are formed by membraned vesicles, contain microRNAs, mRNAs, and proteins.…”

“…10,11 Previous studies have shown that exosomal microRNAs may function as diagnostic biomarkers in numerous malignancies, including MM. 12,13 However, the role of exosomal microRNAs in the progression of MM has not been reported.…”

MicroRNAs and exosomes: Small molecules with big actions in multiple myeloma pathogenesis

“…Two miRNAs‐derived exosomes, miR‐18a and let‐7b, were observed to be considerably associated with poor outcomes of patients regarding the overall and progression‐free survival. Importantly, let‐7b and miR‐18a were predictive in an independent manner even after adjusting for the ISS and particular cytogenetic abnormalities univariate and in multivariate analyses . Exosomes which may contain miRNAs could be secreted from MM cells and regulates expression of genes such as FIH‐1 and HIF‐1 in endothelial cells and promote angiogenesis (Figure ).…”

Emerging roles of noncoding RNAs in multiple myeloma: A review

“…It is worth noting that ncRNAs may alter their expression in patients after treatment and change with MM progression, which gives them the ability to predict the prognosis and drug response. Specific exosomal miRNAs (let‐7b and miR‐18a) were critical in defining worse prognosis in terms of progression‐free survival (PFS) and overall survival (OS) in newly diagnosed MM patients (Manier et al, ). Sometimes, the combination of ncRNAs and other clinicopathological parameters could gain a one‐plus‐one‐greater‐than‐two effect.…”