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

IF 48.8 1区 医学 Q1 CELL BIOLOGY Cancer Cell Pub Date : 2024-07-08 DOI:10.1016/j.ccell.2024.06.003
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, Joaquin Mateo
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Abstract

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.

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用循环肿瘤细胞外囊泡监测转移性前列腺癌基因组学和转录组学演变
肿瘤分泌的胞外囊泡(EVs)在血浆中含量丰富,但它们通过多组学分析来研究肿瘤分子特征的潜力仍未得到广泛开发。从体外和体内转移性前列腺癌(mPC)模型中分离出的循环EV-DNA和EV-RNA的基因组和转录组图谱显示,肿瘤物质对EV载入的DNA/RNA的贡献率很高,这验证了在雄激素受体信号抑制剂(ARSI)或类固醇治疗期间从患者身上收集的两组纵向血浆样本中的发现。EV-DNA基因组特征再现了匹配患者的活检样本和循环肿瘤DNA(ctDNA),并与临床进展相关联。我们开发了一种新方法,可对 EV-RNA 进行转录组分析(RExCuE)。我们报告了循环 EV 的转录组是如何富集肿瘤相关转录本、捕捉某些患者和肿瘤特征并反映治疗中肿瘤适应性变化的。总之,我们的研究表明,EV 分析可对液体活检中的 mPC 进行纵向转录组和基因组分析。
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来源期刊
Cancer Cell
Cancer Cell 医学-肿瘤学
CiteScore
55.20
自引率
1.20%
发文量
179
审稿时长
4-8 weeks
期刊介绍: Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.
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