{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:22Z","timestamp":1785437002426,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/00153"],"award-info":[{"award-number":["PI15\/00153"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PI15\/00153"],"award-info":[{"award-number":["PI15\/00153"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2021SGR052"],"award-info":[{"award-number":["2021SGR052"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2021SGR052"],"award-info":[{"award-number":["2021SGR052"]}],"id":[{"id":"https:\/\/ror.org\/01bg62x04","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Researchers Consolidation Program","doi-asserted-by":"publisher","award":["CES09\/020"],"award-info":[{"award-number":["CES09\/020"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Trabajo y Economia Social","award":["2022-C23.I01.P03.S0020-0000209"],"award-info":[{"award-number":["2022-C23.I01.P03.S0020-0000209"]}]},{"award":["2022-C23.I01.P03.S0020-0000209"],"award-info":[{"award-number":["2022-C23.I01.P03.S0020-0000209"]}],"id":[{"id":"https:\/\/ror.org\/01ccvt456","id-type":"ROR","asserted-by":"publisher"}]},{"name":"European Union\u2014Next Generation EU funds"},{"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>PSA testing plays an important role in the diagnostic workup of prostate cancer; despite this, its cancer specificity is a well-recognised limitation. Consequently, more reliable, non-invasive diagnostic tools that are capable of improving specificity while maintaining sensitivity are needed, thereby enabling better risk stratification, personalised patient management, and reduction in unnecessary invasive procedures. In this study, we characterised the small RNA profile\u2014including miRNAs and tsRNAs\u2014in seminal small extracellular vesicles (sEVs) using high-throughput sequencing to expand biomarker discovery for distinguishing benign from malignant prostate conditions in patients with moderately elevated PSA levels, a setting where non-invasive biomarkers are critically needed. Our analysis confirms a small number of differentially represented sncRNA transcripts contained in seminal sEVs between benign and malignant prostate disease, most of which are of low abundance. This result suggests that shared underlying molecular mechanisms are likely to occur between both prostate disease conditions, especially in patients with moderate PSA levels. Subsequent RT-qPCR analysis revealed differences in expression in PCa compared with healthy controls but not when compared with benign prostatic disease. Given the complexity of the underlying pathophysiological process and the heterogeneity in clinical phenotypes, this limitation was addressed through the application of multivariate approaches (including isomiRs or tRFs), which are proposed as fluid-based biomarkers for prostate cancer, collectively offering improved accuracy and enhancing the negative predictive value of PSA used in clinical settings.<\/jats:p>","DOI":"10.3390\/ijms27146205","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:53:58Z","timestamp":1783932838000},"page":"6205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered sncRNA Signatures in Semen Extracellular Vesicles Between Patients with Benign and Malignant Prostate Disease as Potential Non-Invasive Biomarkers in the PSA Grey Zone"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7099-8168","authenticated-orcid":false,"given":"Adriana","family":"Ferre-Giraldo","sequence":"first","affiliation":[{"name":"Human Molecular Genetics Group, Genes, Disease and Therapy Program-Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Immune-Inflammatory Processes Group, Genes, Disease and Therapy Program-Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7371-5912","authenticated-orcid":false,"given":"Dave","family":"Rojas-Calder\u00f3n","sequence":"additional","affiliation":[{"name":"High Content Genomics and Bioinformatics (HCGB)-Germans Trias I Pujol Research Institute (IGTP), 08916 Badalona, Spain"},{"name":"Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1433 \u00c5s, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2370-2008","authenticated-orcid":false,"given":"Manel","family":"Castells","sequence":"additional","affiliation":[{"name":"Urology Service, Bellvitge University Hospital-ICS (Institut Catal\u00e0 de la Salut), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Raurell","sequence":"additional","affiliation":[{"name":"High Content Genomics and Bioinformatics (HCGB)-Germans Trias I Pujol Research Institute (IGTP), 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-7790","authenticated-orcid":false,"given":"Clara","family":"Mayayo-Vallverd\u00fa","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics Group, Genes, Disease and Therapy Program-Bellvitge Biomedical Research 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