Non‑invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles
Metadatos
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Impact Journals LLC
Materia
Liquid biopsy IsomiRs MiRNA RNA sequencing Extracellular vesicles
Fecha
2016-04-19Referencia bibliográfica
Koppers-Lalic, D., Hackenberg, M., De Menezes, R., Misovic, B., Wachalska, M., Geldof, A., ... & Van Moorselaar, J. (2016). Non-invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles. Oncotarget, 7(16), 22566. [DOI: 10.18632/oncotarget.8124]
Patrocinador
Stichting Urologie 1973; VUmc-CCA; Worldwide Cancer Research (AICR) 15-1005; KWF-VU-5510; Worldwide Cancer Research 15-1005Resumen
In many cancer types, the expression and function of ~22 nucleotide‑long
microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in
extracellular vesicles (EVs) in biofluids, therefore they are considered to have great
potential as biomarkers. In the present study, we investigated whether miRNAs have a
distinct expression pattern in urine‑EVs of prostate cancer (PCa) patients compared to
control males. By next generation sequencing, we determined the miRNA expression
in a discovery cohort of 4 control men and 9 PCa patients. miRNAs were validated by
using a stemloop RT‑PCR in an independent cohort of 74 patients (26 control and 48
PCa‑patients). Whereas standard mapping protocols identified > 10 PCa associated
miRNAs in urinary EVs, miR‑21, miR‑375 and miR‑204 failed to robustly discriminate
for disease in a validation study with RT‑PCR‑detection of mature miRNA sequences. In
contrast, we observed that miRNA isoforms (isomiRs) with 3′ end modifications were
highly discriminatory between samples from control men and PCa patients. Highly
differentially expressed isomiRs of miR‑21, miR‑204 and miR‑375 were subsequently
validated in an independent group of 74 patients. Receiver‑operating characteristic
analysis was performed to evaluate the diagnostic performance of three isomiRs,
resulting in a 72.9% sensitivity with a high (88%) specificity and an area under the
curve (AUC) of 0.866. In comparison, prostate specific antigen had an AUC of 0.707
and measuring the mature form of these miRNAs yielded a lower 70.8% sensitivity
and 72% specificity (AUC 0.766). We propose that isomiRs may carry discriminatory
information which is useful to generate stronger biomarkers.