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.

• Klíčová slova
• NGS, Prostate cancer, diagnosis, miRNA ratio, microRNA, non-invasive, prostate biopsy, regression model, urine,
• MeSH
• biopsie MeSH
• hyperplazie prostaty * genetika   MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery MeSH
• nádory prostaty * genetika   MeSH
• prostata patologie   MeSH
• prostatický specifický antigen MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• MIRN335 microRNA, human MeSH Prohlížeč
• MIRN501 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• prostatický specifický antigen MeSH

Pancreatic cancer (PaC) is one of the most lethal cancers, with an increasing global incidence rate. Unfavorable prognosis largely results from associated difficulties in early diagnosis and the absence of prognostic and predictive biomarkers that would enable an individualized therapeutic approach. In fact, PaC prognosis has not improved for years, even though much efforts and resources have been devoted to PaC research, and the multimodal management of PaC patients has been used in clinical practice. It is thus imperative to develop optimal biomarkers, which would increase diagnostic precision and improve the post-diagnostic management of PaC patients. Current trends in biomarker research envisage the unique opportunity of cell-free microRNAs (miRNAs) present in circulation to become a convenient, non-invasive tool for accurate diagnosis, prognosis and prediction of response to treatment. This review analyzes studies focused on cell-free miRNAs in PaC. The studies provide solid evidence that miRNAs are detectable in serum, blood plasma, saliva, urine, and stool, and that they present easy-to-acquire biomarkers with strong diagnostic, prognostic and predictive potential.

• Klíčová slova
• Cell-free microRNA, diagnosis, non-invasive biomarker, pancreatic cancer, prediction, prognosis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH