RESUMO
Urine of prostate cancer (PCa) carries miRNAs originated from prostate cancer cells as a part of both nucleoprotein complexes and cell-secreted extracellular vesicles. The analysis of such miRNA-markers in urine can be a convenient option for PCa screening. The aims of this study were to reveal miRNA-markers of PCa in urine and design a robust and precise diagnostic test, based on miRNA expression analysis. The expression analysis of the 84 miRNAs in paired urine extracellular vesicles (EVs) and cell free urine supernatant samples from healthy donors, patients with benign and malignant prostate tumours was done using miRCURY LNA miRNA qPCR Panels (Exiqon, Denmark). Sets of miRNAs differentially expressed between the donor groups were found in urine EVs and urine supernatant. Diagnostically significant miRNAs were selected and algorithm of data analysis, based on expression data on 24-miRNA in urine and obtained using 17 analytical systems, was designed. The developed algorithm of data analysis describes a series of steps necessary to define cut-off values and sequentially analyze miRNA expression data according to the cut-offs to facilitate classification of subjects in case/control groups and allows to detect PCa patients with 97.5% accuracy.
Assuntos
MicroRNAs/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Estudos de Casos e Controles , Interpretação Estatística de Dados , Vesículas Extracelulares/genética , Redes Reguladoras de Genes , Humanos , Masculino , MicroRNAs/urina , Pessoa de Meia-Idade , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , Hiperplasia Prostática/urina , Neoplasias da Próstata/urinaRESUMO
Urine of prostate cancer patients contains tumor-specific biopolymers, including protein- and microvesiclesassociated miRNAs that can potentially be used as oncomarkers. Previously we have characterized urine extracellular vesicles and demonstrated diagnostic potential of their miRNA cargo. In this study, we have performed a comparative analysis of the expression of 84 miRNA in paired samples of urine microvesicles and clarified urine from healthy men, patients with benign hyperplasia and cancer of the prostate using miRCURY LNA miRNA qPCR Panels. Subsets of miRNAs with differences in expression between the fractions of the urine were found in all three groups. Two groups of miRNA were identified based on the patterns of their differential expression. They regulate several key signaling pathways associated with prostate cancer development.