Combination of Urinary MiR-501 and MiR-335 With Current Clinical Diagnostic Parameters as Potential Predictive Factors of Prostate Biopsy Outcome

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Authors

JURÁČEK Jaroslav MĄDRZYK Marie TRACHTOVÁ Karolína RUČKOVÁ Michaela BOHOŠOVÁ Júlia BARTH Dominik A. PICHLER Martin STANÍK Michal SLABÝ Ondřej

Year of publication 2023
Type Article in Periodical
Magazine / Source CANCER GENOMICS & PROTEOMICS
MU Faculty or unit

Faculty of Medicine

Citation
Web https://cgp.iiarjournals.org/content/20/3/308
Doi http://dx.doi.org/10.21873/cgp.20383
Keywords Prostate cancer; diagnosis; prostate biopsy; microRNA; urine; non-invasive; NGS; miRNA ratio; regression model
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Description Background: The detection of prostate cancer (PCa) is currently based on prostate-specific antigen (PSA) quantification as an initial screening followed by ultrasound-guided transrectal biopsy. However, the high rate of false-negative biopsies often leads to inappropriate treatment. Therefore, new molecular biomarkers, such as urine microRNAs (miRNAs), are a possible way to redefine PCa diagnostics. Patients and Methods: Urine samples of 356 patients undergoing prostate biopsy (256 cases with confirmed prostate cancer, 100 cases with negative prostate biopsy) at the Masaryk Memorial Cancer Institute (Czech Republic) and additional 36 control subjects (healthy controls, benign prostatic hyperplasia - BPH) were divided into the discovery and validation cohorts and analyzed. In the discovery phase, small RNA sequencing was performed using the QIAseq miRNA Library Kit and the NextSeq 500 platform. Identified miRNA candidates were validated by the RT-qPCR method in the independent validation phase. Results: Using the small RNA sequencing method, we identified 12 urine miRNAs significantly dysregulated between PCa patients and controls. Furthermore, independent validation showed the ability of miR-501-3p and the quantitative miR-335:miR-501 ratio to distinguish between PCa patients and patients with negative prostate biopsy. The subsequent combination of the miR-335:miR-501 ratio with PSA and total prostate volume (TPV) using logistic regression exceeded the analytical accuracy of standalone parameters [area under curve (AUC)=0.75, positive predictive value (PPV)=0.85, negative predictive value (NPV)=0.51)] and discriminated patients according to biopsy outcome. Conclusion: Combination of miR-335:miR-501 ratio with PSA and total prostate volume was able to identify patients with negative prostate biopsy and could potentially streamline decision making for biopsy indication.
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