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Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Prostate Cancer | Research

A preliminary study of micro-RNAs as minimally invasive biomarkers for the diagnosis of prostate cancer patients

Authors: Simona Giglio, Cosimo De Nunzio, Roberto Cirombella, Antonella Stoppacciaro, Omar Faruq, Stefano Volinia, Gustavo Baldassarre, Andrea Tubaro, Hideshi Ishii, Carlo M. Croce, Andrea Vecchione

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Background

A prostate cancer diagnosis is based on biopsy sampling that is an invasive, expensive procedure, and doesn’t accurately represent multifocal disease.

Methods

To establish a model using plasma miRs to distinguish Prostate cancer patients from non-cancer controls, we enrolled 600 patients histologically diagnosed as having or not prostate cancer at biopsy. Two hundred ninety patients were eligible for the analysis. Samples were randomly divided into discovery and validation cohorts.

Results

NGS-miR-expression profiling revealed a miRs signature able to distinguish prostate cancer from non-cancer plasma samples. Of 51 miRs selected in the discovery cohort, we successfully validated 5 miRs (4732-3p, 98-5p, let-7a-5p, 26b-5p, and 21-5p) deregulated in prostate cancer samples compared to controls (p ≤ 0.05). Multivariate and ROC analyses show miR-26b-5p as a strong predictor of PCa, with an AUC of 0.89 (CI = 0.83–0.95;p < 0.001). Combining miRs 26b-5p and 98-5p, we developed a model that has the best predictive power in discriminating prostate cancer from non-cancer (AUC = 0.94; CI: 0,835-0,954).
To distinguish between low and high-grade prostate cancer, we found that miR-4732-3p levels were significantly higher; instead, miR-26b-5p and miR-98-5p levels were lower in low-grade compared to the high-grade group (p ≤ 0.05).
Combining miR-26b-5p and miR-4732-3p we have the highest diagnostic accuracy for high-grade prostate cancer patients, (AUC = 0.80; CI 0,69-0,873).

Conclusions

Noninvasive diagnostic tests may reduce the number of unnecessary prostate biopsies.
The 2-miRs-diagnostic model (miR-26b-5p and miR-98-5p) and the 2-miRs-grade model (miR-26b-5p and miR-4732-3p) are promising minimally invasive tools in prostate cancer clinical management.
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Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:Epub 2019 Jan 8. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:Epub 2019 Jan 8.
2.
go back to reference Boyd LK, Mao X, Lu YJ. The complexity of prostate cancer: genomic alterations and heterogeneity. Nat Rev Urol. 2012;9:652–64.CrossRef Boyd LK, Mao X, Lu YJ. The complexity of prostate cancer: genomic alterations and heterogeneity. Nat Rev Urol. 2012;9:652–64.CrossRef
3.
go back to reference Cary KC, Cooperberg MR. Biomarkers in prostate cancer surveillance and screening: past, present, and future. Ther Adv Urol. 2013;5:318–29.CrossRef Cary KC, Cooperberg MR. Biomarkers in prostate cancer surveillance and screening: past, present, and future. Ther Adv Urol. 2013;5:318–29.CrossRef
4.
go back to reference Saini S. PSA and beyond: alternative prostate cancer biomarkers. Cell Oncol (Dordr). 2016;39:97–106.CrossRef Saini S. PSA and beyond: alternative prostate cancer biomarkers. Cell Oncol (Dordr). 2016;39:97–106.CrossRef
5.
go back to reference Walter LC, Bertenthal D, Lindquist K, Konety BR. PSA screening among elderly men with limited life expectancies. JAMA. 2006;296:2336–42.CrossRef Walter LC, Bertenthal D, Lindquist K, Konety BR. PSA screening among elderly men with limited life expectancies. JAMA. 2006;296:2336–42.CrossRef
6.
go back to reference EAU Guidelines. Edn. presented at the EAU Annual Congress Barcelona 2019. ISBN 978-94-92671-04-2. EAU Guidelines. Edn. presented at the EAU Annual Congress Barcelona 2019. ISBN 978-94-92671-04-2.
7.
go back to reference Abreu AL. The pillars for sustained growth of magnetic resonance imaging pathway for prostate Cancer diagnosis: quality, Reproducibility, Accessibility, Cost Effectiveness, and Training. Eur Urol. 2020. Abreu AL. The pillars for sustained growth of magnetic resonance imaging pathway for prostate Cancer diagnosis: quality, Reproducibility, Accessibility, Cost Effectiveness, and Training. Eur Urol. 2020.
8.
go back to reference Venderink W, Bomers JG, Overduin CG, et al. Multiparametric Magnetic Resonance Imaging for the Detection of Clinically Significant Prostate Cancer: What Urologists Need to Know. Part 3: Targeted Biopsy. Eur Urol. 2019. Venderink W, Bomers JG, Overduin CG, et al. Multiparametric Magnetic Resonance Imaging for the Detection of Clinically Significant Prostate Cancer: What Urologists Need to Know. Part 3: Targeted Biopsy. Eur Urol. 2019.
9.
go back to reference Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst. 2009;101:878–87.CrossRef Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst. 2009;101:878–87.CrossRef
10.
go back to reference D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRef D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRef
11.
go back to reference Fendler A, Stephan C, Yousef GM, et al. The translational potential of microRNAs as biofluid markers of urological tumors. Nat Rev Urol. 2016;13:734–52.CrossRef Fendler A, Stephan C, Yousef GM, et al. The translational potential of microRNAs as biofluid markers of urological tumors. Nat Rev Urol. 2016;13:734–52.CrossRef
12.
go back to reference Mitchell PS, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRef Mitchell PS, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRef
13.
go back to reference Weber JA, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.CrossRef Weber JA, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.CrossRef
14.
go back to reference De Nunzio C, Simone G, Brassetti A, et al. Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study. BMC Cancer. 2016;16:407.CrossRef De Nunzio C, Simone G, Brassetti A, et al. Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study. BMC Cancer. 2016;16:407.CrossRef
15.
go back to reference De Nunzio PF, Lombardo R, et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int. 2016;117(6B):E29–35.CrossRef De Nunzio PF, Lombardo R, et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int. 2016;117(6B):E29–35.CrossRef
16.
go back to reference Panero R, Rinaldi A, Memoli D, et al. iSmaRT: a toolkit for a comprehensive analysis of small RNA-Seq data. Bioinformatics. 2017;33:938–40.CrossRef Panero R, Rinaldi A, Memoli D, et al. iSmaRT: a toolkit for a comprehensive analysis of small RNA-Seq data. Bioinformatics. 2017;33:938–40.CrossRef
17.
go back to reference Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:55.CrossRef Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:55.CrossRef
19.
go back to reference Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis, and therapy. Adv Drug Deliv Rev. 2015;81C:75–93.CrossRef Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis, and therapy. Adv Drug Deliv Rev. 2015;81C:75–93.CrossRef
20.
go back to reference Chen ZH, Zhang GL, Li HR, Luo JD, Li ZX, Chen GM, et al. A panel of five circulating microRNAs as potential biomarkers for prostate cancer. Prostate. 2012;72:1443–52.CrossRef Chen ZH, Zhang GL, Li HR, Luo JD, Li ZX, Chen GM, et al. A panel of five circulating microRNAs as potential biomarkers for prostate cancer. Prostate. 2012;72:1443–52.CrossRef
21.
go back to reference Srivastava A, Goldberger H, Dimtchev A, Marian C, Soldin O, Li X, et al. Circulatory miR-628–5p is downregulated in prostate cancer patients. Tumour Biol. 2014;35:4867–73.CrossRef Srivastava A, Goldberger H, Dimtchev A, Marian C, Soldin O, Li X, et al. Circulatory miR-628–5p is downregulated in prostate cancer patients. Tumour Biol. 2014;35:4867–73.CrossRef
22.
go back to reference McDonald AC, Vira M, Shen J, Sanda M, Raman JD, Liao J, et al. Circulating microRNAs in plasma as potential biomarkers for the early detection of prostate cancer. Prostate. 2018;78:411–8.CrossRef McDonald AC, Vira M, Shen J, Sanda M, Raman JD, Liao J, et al. Circulating microRNAs in plasma as potential biomarkers for the early detection of prostate cancer. Prostate. 2018;78:411–8.CrossRef
23.
go back to reference Haldrup C, Kosaka N, Ochiya T, Borre M, Hoyer S, Orntoft TF, et al. Profiling of circulating microRNAs for prostate cancer biomarker discovery. Drug Deliv Transl Res. 2014;4:19–30.CrossRef Haldrup C, Kosaka N, Ochiya T, Borre M, Hoyer S, Orntoft TF, et al. Profiling of circulating microRNAs for prostate cancer biomarker discovery. Drug Deliv Transl Res. 2014;4:19–30.CrossRef
24.
go back to reference Moltzahn F, Olshen AB, Baehner L, Peek A, Fong L, Stoppler H, et al. Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res. 2011;71:550–60.CrossRef Moltzahn F, Olshen AB, Baehner L, Peek A, Fong L, Stoppler H, et al. Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res. 2011;71:550–60.CrossRef
27.
go back to reference Ni R, Huang Y, Wang J. miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of non-small-cell lung cancer. OncoTargets Ther. 2015;8:2689–97. Ni R, Huang Y, Wang J. miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of non-small-cell lung cancer. OncoTargets Ther. 2015;8:2689–97.
32.
go back to reference Cochetti G, Poli G, Guelfi G, et al. Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: evaluation of potential diagnostic and prognostic role. Onco Targets Ther. 2016;9:7545–7553. Published 2016 Dec 13. doi:https://doi.org/10.2147/OTT.S119027 Cochetti G, Poli G, Guelfi G, et al. Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: evaluation of potential diagnostic and prognostic role. Onco Targets Ther. 2016;9:7545–7553. Published 2016 Dec 13. doi:https://​doi.​org/​10.​2147/​OTT.​S119027
33.
go back to reference Ling XH, Han ZD, Xia D et al. MicroRNA-30c serves as an independent biochemical recurrence predictor and potential tumor suppressor for prostate cancer. Mol Biol Rep. 2014;41:2779–2788). While no data are available for miRs 25-5p and 4732-3p. Ling XH, Han ZD, Xia D et al. MicroRNA-30c serves as an independent biochemical recurrence predictor and potential tumor suppressor for prostate cancer. Mol Biol Rep. 2014;41:2779–2788). While no data are available for miRs 25-5p and 4732-3p.
Metadata
Title
A preliminary study of micro-RNAs as minimally invasive biomarkers for the diagnosis of prostate cancer patients
Authors
Simona Giglio
Cosimo De Nunzio
Roberto Cirombella
Antonella Stoppacciaro
Omar Faruq
Stefano Volinia
Gustavo Baldassarre
Andrea Tubaro
Hideshi Ishii
Carlo M. Croce
Andrea Vecchione
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-01875-0

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