Table 1: Studies investigating the potential of circulating miRNAs as biomarkers of prostate cancer.

Body fluidSample sizeMethodologyKey findingsReference

Plasma25 patients (metastatic PCa), 25 healthy controlsqRT-PCR
(6 miRNAs)
miR-141 levels could differentiate metastatic PCa patients from healthy subjectsMitchell et al., 2008 [36]

Serum6 patients (stages 2–4 PCa), 8 healthy controlsMicroarray (custom) (547 miRNAs)15 miRNAs were elevated in PCa patients. However, serum miRNAs could not distinguish between different cancer typesLodes et al., 2009 [51]

Serum56 patients (20 localized PCa, 20 androgen-dependent PCa, 10 CRPC2), 6 BPH3 controlsqRT-PCR
(miR-21 only)
miR-21 was elevated in CRPC patients compared to BPH and associated with resistance to docetaxel in CRPC patientsZhang et al., 2010 [47]

Serum29 patients (9 low risk, 11 intermediate risk, and 9 high risk)1, 9 healthy controlsqRT-PCR
(384 miRNAs)
10 miRNAs were altered in PCa patients compared to healthy controls. 7 miRNAs were correlated with different risk groups.Moltzahn et al., 2011 [52]

SerumProfiling: 7 high grade, 14 low grade patients. Validation: 116 patients (various grades)qRT-PCR
(667 miRNAs)
miR-141, miR-200b, and miR-375 were elevated in serum from high-grade patients and correlated with clinicopathological parametersBrase et al., 2011 [53]

Plasma21 patients (metastatic PCa)qRT-PCR
(miR-141 only)
miR-141 levels were associated with clinical progression and positively correlated with prostate specific antigenGonzales et al., 2011 [54]

Plasma51 patients (18 localized PCa, 8 local advanced, and 25 metastatic), 20 healthy controlsqRT-PCR (miR-21, miR-141, and miR-221)miR-21 and miR-221 levels were elevated in PCa patients compared to healthy controls. miR-21, miR-141, and miR-221 levels were higher in metastatic compared to localised tumours Agaoglu et al., 2011 [55]

Serum45 patients (37 localized PCa, 8 metastatic), 18 BPH controls, and 20 healthy controlsqRT-PCR (5 miRNAs)miR-26a, miR-195, and let-7i levels were elevated in PCa compared to BPH samplesMahn et al., 2011 [56]

SerumProfiling: 14 TRAMP mice, 14 healthy controls. Validation: 25 patients (metastatic CRPC), 25 healthy controlsMicroarray (Affymetrix; 609 murine miRNAs), qRT-PCR (10 human miRNAs)miR-141, miR-298, miR-346, and miR-375 levels were elevated in metastatic CRPC compared to healthy controls. Expression of miR-375 in primary tumours was associated with biochemical relapse Selth et al., 2012[37]

Plasma, serum, and urineProfiling: 78 patients (various grades, 15 with diagnosed metastases), 28 healthy controls. Validation: 119 patients (47 recurrent after RP4, 72 nonrecurrent)qRT-PCR
(742 miRNAs)
12 circulating miRNAs were at altered levels in PCa patients compared to healthy controls. 16 circulating miRNAs were at altered levels in metastatic versus localised PCa (including miR-141 and miR-375). Urinary levels of miR-107 and miR-574-3p exhibited significant diagnostic valueBryant et al., 2012 [57]

Serum84 patients (28 low risk localised disease, 30 high risk localised disease, and 26 metastatic CRPCqRT-PCR
(667 miRNAs)
miR-375, miR-141, miR-378, and miR-409-3p were at altered levels in metastatic CRPC compared localised cancerNguyen et al., 2013 [58]

PlasmaProfiling: 25 patients (localised and metastatic PCa), 17 BHP controls. Validation: 80 patients (localised and metastatic PCa), 44 BHP controls, and 54 healthy controlsMicroarray (Illumina; 1146 miRNAs), qRT-PCR (8 miRNAs)
(609 murine miRNAs, 10 human miRNAs)
5 miRNAs with significant diagnostic value were identified (let-7c, let-7e, miR-30c, miR-622, and miR-1285)Chen et al., 2012 [59]

Plasma23 patients (15 androgen dependent PCa, 8 CRPC), 20 healthy controlsqRT-PCR
(miR-221 only)
miR-221 was elevated in PCa patients compared to healthy controls, and higher in androgen-dependent PCa compared to CRPCZheng et al., 2012 [60]

Plasma82 patients (various risk scores1,5)qRT-PCR (5 miRNAs)miR-20a, miR-21, miR-145, and miR-221 were associated with tumour risk scores1,5Shen et al., 2012 [61]

Serum72 patients (24 localised prostate cancer, 24 bladder cancer, and 24 renal cell carcinoma), 48 noncancer controlsqRT-PCR (8 putative reference small RNAs and miR-21)SNORD43 may be a suitable reference gene for the analysis of circulating miRNA in patients with urological malignanciesSanders et al., 2012 [62]

“Cancer of the prostate risk assessment” score
2Castration-resistant prostate cancer
3Benign prostatic hyperplasia
4Radical prostatectomy
5D’Amico score