Portal de Periódicos da CAPES

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

2024; Cell Press; Volume: 42; Issue: 7 Linguagem: Inglês

10.1016/j.ccell.2024.06.003

1878-3686

Irene Casanova‐Salas, Daniel Aguilar, Sarai Córdoba-Terreros, Laura Agúndez, Julian Brandariz, Nicolás Herranz, Alba Mas, Macarena González, Rafael Morales‐Barrera, Alexandre Sierra, Mario Soriano‐Navarro, Pablo Cresta, Gisela Mir Arnau, S. Simonetti, Gonçalo Rodrigues, Sara Arce‐Gallego, Luisa Delgado-Serrano, Irene Agustí, Elena Castellano‐Sanz, Richard Mast, Matías de Albert, A. Celma, Anna Santamaría, Lucila González, Natália Castro, Maria del Mar Suanes, Javier Hernández‐Losa, Lara Nonell, Héctor Peinado, Joan Carles, Joaquı́n Mateo,

RNA Research and Splicing

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 in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.