Circulating extracellular vesicles (EVs) present in the bodily fluids of patients with cancer may provide non-invasive access to the tumor tissue. Yet, the transcriptomic lineage of tumor-derived EVs before and after tumor-resection remains poorly understood. Here, we established 60 total small RNA-sequencing profiles from 17 aggressive prostate cancer (PCa) patients tumor and adjacent normal tissue, and EVs isolated from urine, serum, and cancer cell culture media. We interrogated the key satellite alteration in tumor-derived EVs and found that resection of tumor prostate tissue leads to differential expression of reactive oxygen species (ROS), P53 pathways, inflammatory/cytokines, oncogenes, and tumor suppressor genes in the EV nanosatellites. Furthermore, we provide a set of novel EV-specific RNA signature, which are present in cancer but are nonexistent in post-resection patients with undetectable cancer. Finally, using a de novo RNAseq assembly followed by characterization of the small RNA landscape, we found novel small RNA clusters (smRCs) in the EVs, which reside in the unannotated regions. Novel smRCs were orthogonally validated for their differential expression in the biomarker discovery cohort using RT-qPCR. We demonstrate that circulating tumor EVs provide a glimpse of the tumor tissue biology, resolving a major bottleneck in the current liquid biopsy efforts. Secretory vesicles appear to be playing a key role in non-canonical Wnt signaling and miRNA pathways, similar to the circulating tumor cells (CTCs), hence, we propose that such vesicles be called circulating tumor extracellular vesicles (CTEVs).

中文翻译：

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前列腺癌的细胞外囊泡及其肿瘤谱系中的exRNA特征。

存在于癌症患者体液中的循环细胞外囊泡（EVs）可能提供非侵入性进入肿瘤组织的途径。然而，肿瘤切除前后肿瘤源性电动汽车的转录谱系仍然知之甚少。在这里，我们从17位侵袭性前列腺癌（PCa）患者肿瘤和邻近的正常组织以及从尿液，血清和癌细胞培养基中分离出的EV中建立了60个总的小RNA序列。我们询问了肿瘤来源的电动汽车中的关键卫星变化，发现切除肿瘤前列腺组织导致电动汽车纳米卫星中活性氧（ROS），P53途径，炎症/细胞因子，癌基因和肿瘤抑制基因的差异表达。此外，我们提供了一组新颖的EV特异性RNA标记，存在于癌症中，但在无法检测到的切除术后患者中不存在。最后，使用从头RNAseq装配，然后对小RNA格局进行表征，我们在电动汽车中发现了新的小RNA簇（smRCs），它们位于未注释的区域。使用RT-qPCR对新型smRCs在生物标志物发现队列中的差异表达进行了正交验证。我们证明循环的肿瘤电动汽车提供了肿瘤组织生物学的一瞥，解决了当前液体活检工作中的主要瓶颈。与循环肿瘤细胞（CTC）相似，分泌性囊泡似乎在非规范性Wnt信号传导和miRNA途径中起着关键作用，因此，我们建议将这种囊泡称为循环肿瘤细胞外囊泡（CTEV）。