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Clin Chem. 2019 Feb 6. pii: clinchem.2018.296681. doi: 10.1373/clinchem.2018.296681. [Epub ahead of print]

Independent Validation of a Diagnostic Noninvasive 3-MicroRNA Ratio Model (uCaP) for Prostate Cancer in Cell-Free Urine.

Author information

1
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
2
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
3
Exiqon A/S, Vedbaek, Denmark.
4
Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
5
Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.
6
Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
7
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark kdso@clin.au.dk.

Abstract

BACKGROUND:

Detection of prostate cancer (PC) based on serum prostate-specific antigen (PSA) testing leads to many unnecessary prostate biopsies, overdiagnosis, and overtreatment of clinically insignificant tumors. Thus, novel and more accurate molecular biomarkers are required.

METHODS:

Using reverse transcription quantitative PCR, we measured the concentrations of 45 preselected microRNAs (miRNAs) in extracellular vesicle-enriched cell-free urine samples from 4 independent patient cohorts from Spain and Denmark, including 758 patients with clinically localized PC, 289 noncancer controls with benign prostatic hyperplasia (BPH), and 233 patients undergoing initial transrectal ultrasound (TRUS)-guided prostate biopsy owing to PC suspicion (101 with benign and 132 with malignant outcome). Diagnostic potential was assessed by ROC and decision curve analysis.

RESULTS:

We identified and successfully validated 8 upregulated and 21 downregulated miRNAs in urine from PC patients. Furthermore, we validated a previously identified 3-miRNA diagnostic ratio model, uCaP (miR-222-3p*miR-24-3p/miR-30c-5p). High uCaP scores were distinctive of PC in urine samples from BPH vs PC patients in 3 independent cohorts [area under the curve (AUC) = 0.84, 0.71, 0.72]. Additionally, uCaP predicted TRUS biopsy results with greater accuracy than PSA (AUC uCaP = 0.644; AUC PSA = 0.527) for patients within the diagnostic gray zone (PSA ≤ 10 ng/mL).

CONCLUSIONS:

We successfully validated a urine-based diagnostic 3-miRNA signature for PC (uCaP) in 3 independent patient cohorts from 2 countries. In the future, the simple and noninvasive uCaP test may be used to help more accurately select patients for prostate biopsy. Prospective clinical validation is warranted.

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