肿瘤分泌的细胞外囊泡（EV）在血浆中含量丰富，但它们通过多组学分析来探究肿瘤分子特征的潜力尚未得到广泛探索。从转移性前列腺癌 (mPC) 的体外和体内模型中分离出的循环 EV-DNA 和 EV-RNA 的基因组和转录组分析揭示了肿瘤物质对 EV 负载的 DNA/RNA 的高度贡献，验证了两组的研究结果从雄激素受体信号抑制剂（ARSI）或紫杉烷类治疗期间的患者采集纵向血浆样本。 EV-DNA 基因组特征概括了匹配的患者活检和循环肿瘤 DNA (ctDNA)，并与临床进展相关。我们开发了一种新方法来实现 EV-RNA (RExCuE) 的转录组分析。我们报告了循环 EV 的转录组如何丰富肿瘤相关转录本，捕获某些患者和肿瘤特征，并反映治疗中的肿瘤适应变化。总而言之，我们表明 EV 分析能够在液体活检中对 mPC 进行纵向转录组和基因组分析。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.