Assessment of miR-21-5p, miR-451a, and miR-144-3p level in urine in differential diagnosis of localized prostate cancer

Abstract

Background. Limited sensitivity and specificity of existing prostate cancer (PCa) diagnosis methods drive the search for new markers. A number of studies has demonstrated the potential for measuring expression of certain microRNAs in urine.Aim. To evaluate the diagnostic potential of measuring microRNA expression in urine in PCa.Materials and methods. A collection of urine sediment samples from 19 patients with benign prostatic hyperplasia and 44 patients with PCa was analyzed. RNA was isolated using the miRNEasy Serum/Plasma Kit. 16 µL of RNA isolated from each sample were converted into cDNA, which served as a template for real-time polymerase chain reaction. For sequencing, microRNA libraries were prepared using MGIEasy Small RNA Library Prep Kit v.2.0. The formed DNA nanoballs were placed into an MGI DNBSEQ-G400 sequencer. Sequencing results were processed using IsoMiRmap. Differences in microRNA abundance were analyzed using DESeq2. For miRNA-21, high-throughput sequencing data were corroborated by the results of quantitative real-time polymerase chain reaction.Results. 1154 types of microRNA were identified, 11 were differentially represented in all comparison groups. The most significant differences in cell sediment between benign prostatic hyperplasia and PCa patients were recorded for miR-451a (area under the curve (AUC) 0.98). Additionally, the abundance levels of two microRNA isoforms were significantly different: hsa-miR-144-3p|-1 (AUC 0.96) and hsa-miR-21-5p|+4 (AUC 0.68).Сonclusion. This study confirms that altered expression of microRNAs miR-21, miR-451a and miR-144-3p is associated  with PCa, can be detected in urine samples, and can also be a potential non-invasive diagnostic criterion.