The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals
- 1Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
Abstract
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; NCT06981377) at four Italian clinical centers and interrogated data from >10,000 cancer patients' and healthy individuals' samples. 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.
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BibTeX
@misc{vannuccini2026cargo,
title = {{The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals}},
author = {F. Vannuccini and Y. Ciani and V. Mugoni and O. Quaini and F. Orlando and V. Weber and A. C. Martinez and A. Martinelli and E. Biada and A. Marinelli and I. Casanova-Salas and F. Pessina and D. Di Vizio and A. Vannini and P. Cremaschi and S. Lise and C. Nardella and U. De Giorgi and C. Buttigliero and O. Caffo and U. Basso and J. Mateo and G. Attard and F. Demichelis},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.747025},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.747025v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals
AU - F. Vannuccini
AU - Y. Ciani
AU - V. Mugoni
AU - O. Quaini
AU - F. Orlando
AU - V. Weber
AU - A. C. Martinez
AU - A. Martinelli
AU - E. Biada
AU - A. Marinelli
AU - I. Casanova-Salas
AU - F. Pessina
AU - D. Di Vizio
AU - A. Vannini
AU - P. Cremaschi
AU - S. Lise
AU - C. Nardella
AU - U. De Giorgi
AU - C. Buttigliero
AU - O. Caffo
AU - U. Basso
AU - J. Mateo
AU - G. Attard
AU - F. Demichelis
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.747025
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.747025v1
AB - 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; NCT06981377) at four Italian clinical centers and interrogated data from >10,000 cancer patients' and healthy individuals' samples. 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.
ER -