Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution

Autor: Irene Casanova-Salas, Sarai Cordoba-Terreros, Daniel Aguilar, Laura Agundez, Julian Brandariz, Nicolas Herranz, Macarena Gonzalez, Rafael Morales-Barrera, Alexandre Sierra, Mario Soriano-Navarro, Pablo Cresta, Sara Simonetti, Gonçalo Rodrigues, Sara Arce-Gallego, Luisa Delgado-Soriano, Irene Agustí, Elena Castellano-Sanz, Richard Mast, Matias de Albert, Ana Celma, Anna Santamaria, Lucila Gonzalez, Natalia Castro, Maria del Mar Suanes, Javier Hernández-Losa, Lara Nonell, Hector Peinado, Joan Carles, Joaquin Mateo
Rok vydání: 2023
Popis: Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from a range ofin-vitroandin-vivomodels of metastatic prostate cancer (mPC) revealed a high contribution of tumor material to EV-loaded DNA/RNA. Findings were validated in a cohort of longitudinal plasma samples collected from mPC patients during androgen receptor signaling inhibitor (ARSI) therapy. EV-DNA genomic features recapitulated matched-patient biopsies and associated with clinical progression. We developed a novel approach to enable the transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptomic profile in mPC EV-RNA is enriched for tumor-associated transcripts when compared to same patient blood RNA and healthy individuals EV-RNA, and reflect early on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.
Databáze: OpenAIRE