{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:09:04Z","timestamp":1789006144058,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,7]]},"group-title":"Cancer Biology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["22792"],"award-info":[{"award-number":["22792"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"award":["A26822"],"award-info":[{"award-number":["A26822"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Circulating analytes in cancer patients capture tumor-related signals. We profiled matched extracellular vesicle (EV) total RNA and cell-free DNA (cfDNA) from the same plasma aliquots of chemo-naive metastatic castration-resistant prostate cancer (mCRPC) patients treated with Enzalutamide (n=54 patients, n=119 longitudinal samples;\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06981377\">NCT06981377<\/jats:ext-link>\n                  ) at four Italian clinical centers and interrogated data from &gt;10,000 cancer patients\u2019 and healthy individuals\u2019 samples.\n                <\/jats:p>\n                <jats:p>Transcript integrity analysis identified coding and non-coding species with fragmentation patterns varying across RNA biotypes. EV-RNA data deconvolution revealed signal from immune populations, including fractions classified as CD4+ T cells, whose abundance increased with disease progression in plasma EVs and mCRPC tissues. By leveraging tissue data-informed mining, we established a novel prostate cancer-related EV-RNA signature that resulted in an independent predictor of poor prognosis and captured tumor microenvironment-derived signals. Integrating EV-RNA and ctDNA information improved patient stratification for progression-free survival. These findings suggest a multifaceted role for plasma EVs as a source of cancer biomarkers.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of significance<\/jats:title>\n                  <jats:p>EV-RNA provides biologically relevant tumor and immune-derived signals in mCRPC. Integration with cfDNA improves patient stratification, highlighting EVs as a complementary source of translational information for monitoring disease progression and therapeutic response in prostate cancer.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.03.747025","type":"posted-content","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:20:12Z","timestamp":1788823212000},"source":"Crossref","is-referenced-by-count":0,"title":["The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5080-9287","authenticated-orcid":false,"given":"Federico","family":"Vannuccini","sequence":"first","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, 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