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 (Hospital Universitari de Bellvitge)
Castells-Esteve, Manel (Hospital Universitari de Bellvitge)
Sánchez-Herrero, Jose Francisco (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
López-Rodrigo, O. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
De Rocco Ponce, Maurizio (Institut de Recerca Sant Pau)
Bassas, Lluís (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Vigués, Francesc (Hospital Universitari de Bellvitge)
Sumoy, Lauro (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Larriba, Sara (Hospital Universitari de Bellvitge)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI15/00153 Instituto de Salud Carlos III DTS18/00101 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-052
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	5'tRFs ; PSA ; Biomarkers ; Non-invasive diagnosis/prognosis ; Prostate cancer ; Semen extracellular vesicles ; Tsrnas
Published in:	International journal of molecular sciences, Vol. 25 Núm. 18 (september 2024) , p. 10122, ISSN 1422-0067

DOI: 10.3390/ijms251810122
PMID: 39337607

24 p, 4.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles