Abstract 5251
Background
Prostate cancer (PCa) is one of the major cancers in men, but discrepancy between incidence and mortality calls for a careful approach to screening and diagnosis. Controversy between US Preventive Services Task Force recommendations and the outcomes clinical trials illustrate that the shortcomings of existing biomarkers and high demand in novel approaches for prostate cancer screening. Recent studies have suggested miRNAs as new candidates for cancer biomarkers. In this study, we have investigated the use of miRNAs found in cell-free nucleoprotein complexes and urine extracellular vesicles (EVs) as prostate cancer biomarkers.
Methods
Urine extracellular vesicles were isolated by standard ultracentrifugation protocols. Cell-free supernatant containing nucleoprotein complexes was obtained after 17.000g centrifugation. miRNA from supernatant and urine EVs were isolated as described previously (Lekchnov et al, Anal Biochem, 2016) and profiled using customized miRCURY LNA miRNA qPCR panels (Exiqon Ltd).
Results
Profiling of the expression of 84 miRNAs in paired samples of urine supernatant and urine EVs of 10 healthy donors (HD), 10 PCa patients and 10 patients with benign prostatic hyperplasia (BPH) has identified subsets of miRNAs differentially expressed between the groups. Using ratio-based normalization miRNA pairs with significantly different expression were selected and verified in an independent sample of 15 HD, 15 PCa and 15 BPH patients. To facilitate highly specific PCa detection a stepwise diagnostic algorithm based on miRNA expression in HD group (median ± 2SD cut off values) and hierarchical analysis of analytical systems was proposed (Bryzgunova et al, PLoS One, 2019). Diagnostic panels developed using miRNA profiling data and comprised of 24 miRNAs (17 miRNA ratios) could classify PCa and BPH patients and HD with 100% specificity and 97.5% accuracy. Diagnostic system based on the expression of 5 miRNA pairs in urine (miR-30a: miR-125b, miR-425: miR-331, miR-29b: miR-21, miR-191: miR-200a, miR-331: miR-106b) can be potentially used to identify PCa.
Conclusions
The data shows promise of urine cell-free and vesicle cargo miRNA as prostate cancer biomarkers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The study was supported by the Russian Science Foundation (no. 16-15-00124). Pavel P. Laktionov acknowledges financial support within the framework of the Russian state funded budget project # АААА-А17-117020210026-2 to the ICBFM SB RAS.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5444 - Analysis of the tumor microenvironment and tumor genotype through different stages of lung adenocarcinoma
Presenter: Peter Zink
Session: Poster Display session 1
Resources:
Abstract
3124 - Does Progress achieved in the Treatment of Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) reach the Elderly Population?
Presenter: Jorune Suipyte
Session: Poster Display session 1
Resources:
Abstract
5142 - Prognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)
Presenter: Yoshihito Ohhara
Session: Poster Display session 1
Resources:
Abstract
1580 - A novel risk classification system based on nomogram scores to predict survival of patients presenting with brain metastases at the first diagnosis of NSCLC
Presenter: Pengfei Cui
Session: Poster Display session 1
Resources:
Abstract
4442 - Comparison of real-world response rate (rwRR) to RECIST-based response rate in patients with advanced non-small cell lung cancer (aNSCLC)
Presenter: Xinran Ma
Session: Poster Display session 1
Resources:
Abstract
5405 - Estimating the cost and survival impact of new aNSCLC therapies in Canada with the iTEN model
Presenter: Parneet Kaur Cheema
Session: Poster Display session 1
Resources:
Abstract
1893 - SMARCA4 Deficient Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Genomic Profiling (CGP) Study
Presenter: Stephen Graziano
Session: Poster Display session 1
Resources:
Abstract
5582 - Exploring Resistance to Nivolumab [NIV] applying an Immune Genomic Signature (IGS) in advanced pretreated NSCLC [PRINCiPe study]
Presenter: Sara Pilotto
Session: Poster Display session 1
Resources:
Abstract
1408 - DNA damage repair deficiency is associated with early resistance to crizotinib: whole-genome analysis in non-small cell lung cancer patients with ALK-fusion
Presenter: Dongyun He
Session: Poster Display session 1
Resources:
Abstract
5751 - Phase 3 ALTA-3 study of brigatinib (BRG) vs alectinib (ALC) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)−positive non–small cell lung cancer (NSCLC) that progressed on crizotinib (CRZ)
Presenter: Sanjay Popat
Session: Poster Display session 1
Resources:
Abstract