- EV profiling enables longitudinal interrogation of metastatic PC using liquid biopsy
- EV-DNA genomic profiling recapitulates tumor features and associates with progression
- RExCuE allows mRNA analysis in circulating EVs for liquid biopsies transcriptomic profiling
- EV-RNA indicates early tumor adaptation changes during therapy in a non-invasive manner
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.
- Irene Casanova-Salas, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Daniel Aguilar, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Sarai Cordoba-Terreros, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laura Agundez, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Julian Brandariz, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Nicolas Herranz, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Alba Mas, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Macarena Gonzalez, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Rafael Morales-Barrera, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Alexandre Sierra, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Mario Soriano-Navarro, Principe Felipe Research Institute (CIPF), Valencia, Spain
- Pablo Cresta, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Gisela Mir, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Sara Simonetti, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Gonçalo Rodrigues, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Sara Arce-Gallego, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Luisa Delgado-Serrano, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Irene Agustí, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Elena Castellano-Sanz, Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain
- Richard Mast, Vall d’Hebron University Hospital, Barcelona, Spain
- Matias de Albert, Vall d’Hebron University Hospital, Barcelona, Spain
- Ana Celma, Vall d’Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Anna Santamaria, Vall d’Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Lucila Gonzalez, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Natalia Castro, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Maria del Mar Suanes, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Javier Hernández-Losa, Vall d’Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Lara Nonell, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Hector Peinado, Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain
- Joan Carles, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Joaquin Mateo, Vall d’Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
Circulating Tumor Extracellular Vesicles to Monitor Metastatic Prostate Cancer Genomics and Transcriptomic Evolution