Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers
| Autor: | Xiaobo Liang, Jon B. Klein, Kathleen A. Neville, Atif A. Ahmed, Safinur Atay, Vincent S. Staggs, Jennifer Crow, Michael L. Merchant, Kris Laurence, Devin C. Koestler, Andrew K. Godwin, Glenson Samuel, Emily Nissen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
business.industry CD99 biomarkers exosomes Extracellular vesicle Proteomics medicine.disease Malignancy Microvesicles 03 medical and health sciences 030104 developmental biology 0302 clinical medicine EWS-ETS Oncology 030220 oncology & carcinogenesis Proteome Cancer research Biomarker (medicine) Medicine Sarcoma extracellular vesicles business Ewing sarcoma Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Purpose Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs). Materials and methods We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and identified 619 proteins composing the core ESFT sEV proteome. We compared these core proteins to databases of common plasma-based proteins and sEV-associated proteins found within healthy plasma to identify proteins unique or enriched within ESFT. Results From these analyses, two membrane bound proteins with biomarker potential were selected, CD99/MIC2 and NGFR, to develop a liquid-based assay enriching of ESFT-associated sEVs and detection of sEV mRNA cargo (i.e., EWS-ETS transcripts). We employed this immuno-enrichment approach to diagnosis of ESFT utilizing plasma (250 μl) from both localized and metastatic ESFT pediatric patients and cancer-free controls, and showed significant diagnostic power [AUC = 0.92, p = 0.001 for sEV numeration, with a PPV = 1.00, 95% CI = (0.63, 1.00) and a NPV = 0.67, 95% CI = (0.30, 0.93)]. Conclusions In this study, we demonstrate utilization of circulating ESFT-associated sEVs in pediatric patients as a source of minimally invasive diagnostic and potentially prognostic biomarkers. |
| Databáze: | OpenAIRE |
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