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
3157 - Efficacy and safety of anlotinib in advanced leiomyosarcoma: Subgroup analysis of a phase IIB trial (ALTER0203)
Presenter: Yihebali Chi
Session: Poster Display session 1
Resources:
Abstract
3710 - The effect of treatment line on the efficacy of Anlotinib hydrochloride in advanced alveolar soft part sarcoma patients
Presenter: Zhiwei Fang
Session: Poster Display session 1
Resources:
Abstract
3184 - Prior exposure to pazopanib (PAZ) did not minor efficacy of regorafenib (REG) in non-adipocytic soft tissue sarcoma patients (pts)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
798 - Pexidartinib (Pex) for locally advanced tenosynovial giant cell tumor (TGCT): characterization of hepatic adverse reactions (ARs)
Presenter: Sebastian Bauer
Session: Poster Display session 1
Resources:
Abstract
6117 - VEGFR2 and ITGA polymorphisms as novel pan-sarcoma biomarkers for sensitivity prediction as well as toxicity prevention anti-angiogenesis therapy in pediatric and young adult
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
5450 - Reversion of resistance to mTOR inhibitors with the addition of exemestane in patients with malignant PEComa.
Presenter: Roberta Sanfilippo
Session: Poster Display session 1
Resources:
Abstract
4279 - Efficacy and Safety of VEGFR2 Inhibitor Apatinib combined with chemotherapy for Sarcoma in Stage IV
Presenter: Zhiwu Ren
Session: Poster Display session 1
Resources:
Abstract
5929 - Outcomes of metastatic soft tissue sarcoma treated with Pazopanib from dedicated medical oncology sarcoma clinic: A holistic care approach from a developing country
Presenter: Akhil Kapoor
Session: Poster Display session 1
Resources:
Abstract
2469 - Inhibition of mTOR signaling enhances Trabectedin activity in Soft Tissue Sarcoma
Presenter: David Moura
Session: Poster Display session 1
Resources:
Abstract
4210 - Efficacy and safety of apatinib for advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib: An open-label, multicenter, single-arm, phase II trial
Presenter: Zhaolun Cai
Session: Poster Display session 1
Resources:
Abstract