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Prognostic role of circulating exosomal miRNAs in multiple myeloma
Salomon Manier1,2,3, Chia-Jen Liu1,4,5, Hervé Avet-Loiseau6
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
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.
Insights
Circulating exosomal microRNAs (miRNAs) show prognostic significance in multiple myeloma (MM). Specific miRNAs, let-7b and miR-18a, predict progression-free and overall survival in newly diagnosed MM patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Exosomes are key intercellular communicators, implicated in cancer progression.
- Circulating exosomal microRNAs (miRNAs) are emerging biomarkers for various diseases.
- Multiple myeloma (MM) diagnosis and prognosis require improved molecular markers.
Purpose of the Study:
- To investigate the prognostic value of circulating exosomal miRNAs in patients with newly diagnosed multiple myeloma (MM).
- To identify specific exosomal miRNAs associated with progression-free survival (PFS) and overall survival (OS) in MM.
Main Methods:
- Small RNA sequencing was performed on exosomes from 10 MM patients and healthy controls.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) array analysis of 22 miRNAs was conducted on serum exosomes from 156 newly diagnosed MM patients.
- Statistical analyses, including univariate and multivariate analyses, were used to correlate miRNA levels with patient outcomes.
Main Results:
- MicroRNAs (miRNAs) were identified as the predominant small RNAs within circulating exosomes.
- Two specific miRNAs, let-7b and miR-18a, were significantly associated with both PFS and OS in univariate analysis.
- These miRNAs remained statistically significant predictors of PFS and OS in multivariate analysis, even after adjusting for the International Staging System and adverse cytogenetics.
Conclusions:
- Circulating exosomal miRNAs, specifically let-7b and miR-18a, can serve as valuable prognostic biomarkers in newly diagnosed multiple myeloma (MM).
- These findings support the potential of exosomal miRNAs for improved risk stratification and identification of MM patients with poor outcomes.
- Further validation in independent prospective cohorts is warranted to confirm these prognostic implications.
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