The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals

Résumé fourni par la source

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. Statement of significance 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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.