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BMC Cancer. 2017 Nov 9;17(1):730. doi: 10.1186/s12885-017-3737-z.

Detection of circulating miRNAs: comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients.

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Latvian Biomedical Research and Study Centre, Ratsupites Str 1, k-1, Riga, LV-1067, Latvia.
Riga Stradiņš University, Dzirciema Str 16, Riga, LV-1007, Latvia.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379, Oslo, Norway.
Institute of Clinical and Preventive Medicine, Faculty of Medicine, University of Latvia, Raina blvd. 19, Riga, LV - 1586, Latvia.
Latvian Biomedical Research and Study Centre, Ratsupites Str 1, k-1, Riga, LV-1067, Latvia.



Circulating cell-free miRNAs have emerged as promising minimally-invasive biomarkers for early detection, prognosis and monitoring of cancer. They can exist in the bloodstream incorporated into extracellular vesicles (EVs) and ribonucleoprotein complexes. However, it is still debated if EVs contain biologically meaningful amounts of miRNAs and may provide a better source of miRNA biomarkers than whole plasma. The aim of this study was to systematically compare the diagnostic potential of prostate cancer-associated miRNAs in whole plasma and in plasma EVs.


RNA was isolated from whole plasma and plasma EV samples from a well characterised cohort of 50 patient with prostate cancer (PC) and 22 patients with benign prostatic hyperplasia (BPH). Nine miRNAs known to have a diagnostic potential for PC in cell-free blood were quantified by RT-qPCR and the relative quantities were compared between patients with PC and BPH and between PC patients with Gleason score ≥ 8 and ≤6.


Only a small fraction of the total cell-free miRNA was recovered from the plasma EVs, however the EV-incorporated and whole plasma cell-free miRNA profiles were clearly different. Four of the miRNAs analysed showed a diagnostic potential in our patient cohort. MiR-375 could differentiate between PC and BPH patients when analysed in the whole plasma, while miR-200c-3p and miR-21-5p performed better when analysed in plasma EVs. EV-incorporated but not whole plasma Let-7a-5p level could distinguish PC patients with Gleason score ≥ 8 vs ≤6.


This study demonstrates that for some miRNA biomarkers EVs provide a more consistent source of RNA than whole plasma, while other miRNAs show better diagnostic performance when tested in the whole plasma.


Biomarkers; Cell-free miRNAs; Exosomes; Extracellular vesicles; Liquid biopsy; Microvesicles; Prostate cancer

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