exRNA Signatures in Extracellular Vesicles and their Tumor-Lineage from Prostate Cancer
exRNA Signatures in Extracellular Vesicles and their Tumor-Lineage from Prostate Cancer
Abstract 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) patient’s 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).
Tewari Ashutosh K.、Stolovitzky Gustavo、Han Dan、Wunsch Benjamin H.、Nair Sujit、Smith Melissa、Sebra Robert P.、Sahoo Susmita、Yadav Kamlesh K.、Kozlova Edgar EG、Gifford Stacey M.、Losic Bojan、Ahsen Mehmet E.、Smith Joshua T.、Gordon Ronald E.、Vlachos Konstantinos、Chen Tzu-yi、Olsen Reena、Dogra Navneet、Bhatt Kamala、Allette Kimaada、Margolin Adam、Weil Rachel、Cordon-Cardo Carlos、Kim Sung-Cheol
Department of Urology, Icahn School of Medicine at Mount SinaiIBM T. J. Watson Research Center, Yorktown Heights||Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Oncology Sciences and Pathology, Icahn School of Medicine at Mount SinaiIBM T. J. Watson Research Center, Yorktown HeightsDepartment of Urology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Cardiology, Icahn School of Medicine at Mount SinaiDepartment of Urology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiIBM T. J. Watson Research Center, Yorktown HeightsDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiIBM T. J. Watson Research Center, Yorktown HeightsDepartment of Oncology Sciences and Pathology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Oncology Sciences and Pathology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai||Department of Oncology Sciences and Pathology, Icahn School of Medicine at Mount Sinai||IBM T. J. Watson Research Center, Yorktown HeightsDepartment of Urology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Urology, Icahn School of Medicine at Mount SinaiDepartment of Oncology Sciences and Pathology, Icahn School of Medicine at Mount SinaiIBM T. J. Watson Research Center, Yorktown Heights
肿瘤学生物科学研究方法、生物科学研究技术分子生物学
Extracellular vesicles (EVs)exosomestumorRNA sequencingprostate cancerliquid biopsy
Tewari Ashutosh K.,Stolovitzky Gustavo,Han Dan,Wunsch Benjamin H.,Nair Sujit,Smith Melissa,Sebra Robert P.,Sahoo Susmita,Yadav Kamlesh K.,Kozlova Edgar EG,Gifford Stacey M.,Losic Bojan,Ahsen Mehmet E.,Smith Joshua T.,Gordon Ronald E.,Vlachos Konstantinos,Chen Tzu-yi,Olsen Reena,Dogra Navneet,Bhatt Kamala,Allette Kimaada,Margolin Adam,Weil Rachel,Cordon-Cardo Carlos,Kim Sung-Cheol.exRNA Signatures in Extracellular Vesicles and their Tumor-Lineage from Prostate Cancer[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2020.09.28.20190009.点此复制
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