Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies

Introduction: Extracellular vesicles (EVs) have emerged as a very attractive source of cancer- derived RNA biomarkers for the early detection, prognosis and monitoring of various cancers, including prostate cancer (PC). However, biofluids contain a mixture of EVs released from a variety of tissues a...

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Main Authors: Cristina Bajo-Santos, Agnese Brokāne, Pawel Zayakin, Edgars Endzeliņš, Kristīne Soboļevska, Alberts Belovs, Juris Jansons, Māris Sperga, Alicia Llorente, Ilze Radoviča-Spalviņa, Vilnis Lietuvietis, Aija Linē
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.980433/full
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author Cristina Bajo-Santos
Agnese Brokāne
Pawel Zayakin
Edgars Endzeliņš
Kristīne Soboļevska
Alberts Belovs
Juris Jansons
Māris Sperga
Alicia Llorente
Alicia Llorente
Ilze Radoviča-Spalviņa
Vilnis Lietuvietis
Aija Linē
author_facet Cristina Bajo-Santos
Agnese Brokāne
Pawel Zayakin
Edgars Endzeliņš
Kristīne Soboļevska
Alberts Belovs
Juris Jansons
Māris Sperga
Alicia Llorente
Alicia Llorente
Ilze Radoviča-Spalviņa
Vilnis Lietuvietis
Aija Linē
author_sort Cristina Bajo-Santos
collection DOAJ
description Introduction: Extracellular vesicles (EVs) have emerged as a very attractive source of cancer- derived RNA biomarkers for the early detection, prognosis and monitoring of various cancers, including prostate cancer (PC). However, biofluids contain a mixture of EVs released from a variety of tissues and the fraction of total EVs that are derived from PC tissue is not known. Moreover, the optimal biofluid—plasma or urine—that is more suitable for the detection of EV- enclosed RNA biomarkers is not yet clear.Methodology: In the current study, we performed RNA sequencing analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer.Results and Discussion: The most abundant RNA biotypes in EVs were miRNA, piRNA, tRNA, lncRNA, rRNA and mRNA. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype. The levels of 63 mRNAs, 3 lncRNAs, 2 miRNAs and 1 piRNA were significantly increased in the tumors and decreased in the post-operation urinary EVs, thus suggesting that these RNAs mainly originate from PC tissue. No such RNA biomarkers were identified in plasma EVs. This suggests that the fraction of PC-derived EVs in urine is larger than in plasma and allows the detection and tracking of PC-derived RNAs.
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spelling doaj.art-56f25fa01f404eb0a6b3622f50247a7d2023-02-03T04:33:42ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-02-011010.3389/fmolb.2023.980433980433Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsiesCristina Bajo-Santos0Agnese Brokāne1Pawel Zayakin2Edgars Endzeliņš3Kristīne Soboļevska4Alberts Belovs5Juris Jansons6Māris Sperga7Alicia Llorente8Alicia Llorente9Ilze Radoviča-Spalviņa10Vilnis Lietuvietis11Aija Linē12Latvian Biomedical Research and Study Centre, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaRiga Stradiņš University, Riga, LatviaRiga Stradiņš University, Riga, LatviaRiga Stradiņš University, Riga, LatviaDepartment Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayDepartment for Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, NorwayGenera Ltd., Riga, LatviaRiga Stradiņš University, Riga, LatviaLatvian Biomedical Research and Study Centre, Riga, LatviaIntroduction: Extracellular vesicles (EVs) have emerged as a very attractive source of cancer- derived RNA biomarkers for the early detection, prognosis and monitoring of various cancers, including prostate cancer (PC). However, biofluids contain a mixture of EVs released from a variety of tissues and the fraction of total EVs that are derived from PC tissue is not known. Moreover, the optimal biofluid—plasma or urine—that is more suitable for the detection of EV- enclosed RNA biomarkers is not yet clear.Methodology: In the current study, we performed RNA sequencing analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer.Results and Discussion: The most abundant RNA biotypes in EVs were miRNA, piRNA, tRNA, lncRNA, rRNA and mRNA. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype. The levels of 63 mRNAs, 3 lncRNAs, 2 miRNAs and 1 piRNA were significantly increased in the tumors and decreased in the post-operation urinary EVs, thus suggesting that these RNAs mainly originate from PC tissue. No such RNA biomarkers were identified in plasma EVs. This suggests that the fraction of PC-derived EVs in urine is larger than in plasma and allows the detection and tracking of PC-derived RNAs.https://www.frontiersin.org/articles/10.3389/fmolb.2023.980433/fullextracellular vesiclesliquid biopsyRNA biotypesRNA sequencingdigital droplet PCRprostate cancer
spellingShingle Cristina Bajo-Santos
Agnese Brokāne
Pawel Zayakin
Edgars Endzeliņš
Kristīne Soboļevska
Alberts Belovs
Juris Jansons
Māris Sperga
Alicia Llorente
Alicia Llorente
Ilze Radoviča-Spalviņa
Vilnis Lietuvietis
Aija Linē
Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
Frontiers in Molecular Biosciences
extracellular vesicles
liquid biopsy
RNA biotypes
RNA sequencing
digital droplet PCR
prostate cancer
title Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
title_full Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
title_fullStr Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
title_full_unstemmed Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
title_short Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies
title_sort plasma and urinary extracellular vesicles as a source of rna biomarkers for prostate cancer in liquid biopsies
topic extracellular vesicles
liquid biopsy
RNA biotypes
RNA sequencing
digital droplet PCR
prostate cancer
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.980433/full
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