Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels

PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles...

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Autores: Ferre Giraldo, Adriana, Castells, Manel, Sánchez Herrero, José Francisco, López Rodrigo, Olga, Rocco Ponce, Maurizio De, Bassas, Lluís, Vigués, Francesc, Sumoy, Lauro, Larriba, Sara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/216515
Acceso en línea:https://hdl.handle.net/2445/216515
Access Level:acceso abierto
Palabra clave:Càncer de pròstata
Semen
Diagnòstic
Pronòstic mèdic
Prostate cancer
Diagnosis
Prognosis
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spelling Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA LevelsFerre Giraldo, AdrianaCastells, ManelSánchez Herrero, José FranciscoLópez Rodrigo, OlgaRocco Ponce, Maurizio DeBassas, LluísVigués, FrancescSumoy, LauroLarriba, SaraCàncer de pròstataSemenDiagnòsticPronòstic mèdicProstate cancerSemenDiagnosisPrognosisPSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5 ' tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5 '-tRNA-Glu-TTC-9-1_L30 and 5 '-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score >= 7 and staging disease beyond IIA, supporting that the 5 ' tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5 ' tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.MDPI2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/216515Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ijms251810122International Journal of Molecular Sciences, 2024, vol. 25, num. 18https://doi.org/10.3390/ijms251810122cc-by (c) Ferre Giraldo, Adriana et al., 2024http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2165152026-05-27T06:46:51Z
dc.title.none.fl_str_mv Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
title Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
spellingShingle Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
Ferre Giraldo, Adriana
Càncer de pròstata
Semen
Diagnòstic
Pronòstic mèdic
Prostate cancer
Semen
Diagnosis
Prognosis
title_short Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
title_full Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
title_fullStr Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
title_full_unstemmed Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
title_sort Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
dc.creator.none.fl_str_mv Ferre Giraldo, Adriana
Castells, Manel
Sánchez Herrero, José Francisco
López Rodrigo, Olga
Rocco Ponce, Maurizio De
Bassas, Lluís
Vigués, Francesc
Sumoy, Lauro
Larriba, Sara
author Ferre Giraldo, Adriana
author_facet Ferre Giraldo, Adriana
Castells, Manel
Sánchez Herrero, José Francisco
López Rodrigo, Olga
Rocco Ponce, Maurizio De
Bassas, Lluís
Vigués, Francesc
Sumoy, Lauro
Larriba, Sara
author_role author
author2 Castells, Manel
Sánchez Herrero, José Francisco
López Rodrigo, Olga
Rocco Ponce, Maurizio De
Bassas, Lluís
Vigués, Francesc
Sumoy, Lauro
Larriba, Sara
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de pròstata
Semen
Diagnòstic
Pronòstic mèdic
Prostate cancer
Semen
Diagnosis
Prognosis
topic Càncer de pròstata
Semen
Diagnòstic
Pronòstic mèdic
Prostate cancer
Semen
Diagnosis
Prognosis
description PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5 ' tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5 '-tRNA-Glu-TTC-9-1_L30 and 5 '-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score >= 7 and staging disease beyond IIA, supporting that the 5 ' tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5 ' tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/216515
url https://hdl.handle.net/2445/216515
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms251810122
International Journal of Molecular Sciences, 2024, vol. 25, num. 18
https://doi.org/10.3390/ijms251810122
dc.rights.none.fl_str_mv cc-by (c) Ferre Giraldo, Adriana et al., 2024
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ferre Giraldo, Adriana et al., 2024
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404107150721024
score 15.812455

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