MicroRNAs from urinary exosomes as alternative biomarkers in the differentiation of benign and malignant prostate diseases

Abstract

Introduction: Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth most cancer-related cause of death worldwide. Various tools are used in the diagnosis of PCa, such as the Prostate-Specific Antigen (PSA) value or digital rectal examination. A final differentiation from benign prostate diseases such as benign prostatic hyperplasia (BPH) can often only be made by a transrectal prostate biopsy. This procedure carries post-procedural complications for the patients and may lead to hospitalization. Urinary exosomes contain unique components, such as microRNAs (miRNAs) with information about their original tissue. As miRNAs appear to play a role in the development of PCa, they might be useful to develop procedures that could potentially make transrectal biopsies avoidable in certain situations. Methods: The current study aimed to investigate whether miRNAs from urinary exosomes can be used to differentiate PCa from BPH. For this purpose, urine samples from 28 patients with PCa and 25 patients with BPH were collected and analysed using next-generation sequencing to obtain expression profiles. Results and conclusion: The two miRNAs hsa-miR-532-3p and hsa-miR-6749-5p showed a significant differential expression within the group of patients with PCa in a training subset of the data containing 32 patients. They were further validated on the independent test data subset containing 20 patients. Additionally, a machine learning algorithm was used to generate a miRNA pattern to distinguish the two disease entities. Both approaches seem to be suitable for the search of alternative diagnostic tools for the differentiation of benign and malignant prostate diseases.

Post‐prostatic‐massage urine exosomes of men with chronic prostatitis/chronic pelvic pain syndrome carry prostate‐cancer‐typical microRNAs and activate proto‐oncogenes

“…Among others, these pathways contain several factors involved in the regulation of growth factors, cytokine-cytokine receptor interaction, apoptosis, cell cycle progression, cellular migration and invasion, and transcriptional regulation. MicroRNAs from urinary exosomes have already been suggested as alternative biomarkers in the differentiation of benign and malignant prostate diseases [51]. Our results suggest that microRNAs from PPM urine of CP/CPPS may be early prognostic biomarkers of malignant transformation of the prostate.…”

“…Further, KEGG pathway analyses revealed that putative target genes of CP/CPPS‐specific upregulated microRNAs were significantly enriched for cancer‐associated pathways, such as “Prostate cancer,” “MAPK signaling pathway,” “FoxO signaling pathway,” and “Non‐small cell lung cancer.” Among others, these pathways contain several factors involved in the regulation of growth factors, cytokine–cytokine receptor interaction, apoptosis, cell cycle progression, cellular migration and invasion, and transcriptional regulation. MicroRNAs from urinary exosomes have already been suggested as alternative biomarkers in the differentiation of benign and malignant prostate diseases [ 51 ]. Our results suggest that microRNAs from PPM urine of CP/CPPS may be early prognostic biomarkers of malignant transformation of the prostate.…”

Urinary microRNA profiling in pregnant women identifies placental microRNAs that are candidate biomarkers for monitoring placental health

“…Only limited medical fields have investigated urinary microRNA profiles. Examples are metabolic diseases, chronic kidney disease, and cancers such as clear cell renal cell carcinoma, and prostate cancer [8,13–16]. The main innovation of this study was to explore urinary microRNAs as a novel resource to be potentially utilized for monitoring the pregnancy course.…”

“…Only limited medical fields have investigated urinary microRNA profiles. Examples are metabolic diseases, chronic kidney disease, and cancers such as clear cell renal cell carcinoma, and prostate cancer [8,[13][14][15][16].…”

Improving the Diagnostic Potential of Extracellular miRNAs Coupled to Multiomics Data by Exploiting the Power of Artificial Intelligence

“…For urinary miRNAs, the majority of papers are related to cancer biomarker discovery (i.e., prostate cancers) and to the identification of small RNAs or miRNAs able to discriminate, for example, prostate cancers from benign prostate hyperplasia (BPH). In fact, Markert and collaborators used the random forest method to identify candidate small RNAs ( Markert et al, 2021 ), and in other studies the same group focused on miRNAs ( Holdmann et al, 2022 ).…”