Abstract
BackgroundCirculating 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.MethodsRNA 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.ResultsOnly 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.ConclusionsThis 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.
Highlights
Circulating cell-free miRNAs have emerged as promising minimally-invasive biomarkers for early detection, prognosis and monitoring of cancer
MiR-21-5p, miR-200c-3p, miR-210-3p and miR-375 have been shown to be increased in the blood of prostate cancer (PC) patients as compared to benign prostatic hyperplasia (BPH) or healthy controls consistently by two or more studies, while miR-30c-5p and miR-223-3p were found to be consistently decreased in the blood of PC patients
transmission electron microscopy (TEM) images revealed that the majority of particles were ranging in size from 25 to 60 nm that corresponds to the size of exosomes (Fig. 1b)
Summary
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. The aim of this study was to systematically compare the diagnostic potential of prostate cancer-associated miRNAs in whole plasma and in plasma EVs. Circulating cell-free micro-RNAs (miRNAs) have emerged as promising biomarkers for the development of bloodbased assays for early detection, prognosis and monitoring of cancer. The greatest unmet clinical needs in the management of PC are sensitive and reliable noninvasive tools for differentiating between PC and benign prostatic diseases, and between potentially fast progressing PC requiring aggressive treatment and a relatively indolent disease that can be managed by active surveillance
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