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.
Cancer cell. 2024 Jul 08 [Epub]
Irene Casanova-Salas, Daniel Aguilar, Sarai Cordoba-Terreros, Laura Agundez, Julian Brandariz, Nicolas Herranz, Alba Mas, Macarena Gonzalez, Rafael Morales-Barrera, Alexandre Sierra, Mario Soriano-Navarro, Pablo Cresta, Gisela Mir, Sara Simonetti, Gonçalo Rodrigues, Sara Arce-Gallego, Luisa Delgado-Serrano, 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
Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Vall d'Hebron University Hospital, Barcelona, Spain., Principe Felipe Research Institute (CIPF), Valencia, Spain., Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain., Vall d'Hebron University Hospital, Barcelona, Spain., Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Vall d'Hebron University Hospital, Barcelona, Spain., Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Vall d'Hebron University Hospital, Barcelona, Spain. Electronic address: .