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Extracellular vesicles are secreted by all cell types and are currently established to some extent as representatives of the cell of origin. The present study characterized and evaluated the diagnostic and prognostic potential of plasma extracellular vesicles (EVs) proteome in DLBCL by using state-of-the-art mass spectrometry. The EV proteome is strongly affected by DLBCL status, with multiple proteins uniquely identified in the plasma of DLBCL. A proof-of-concept classifier resulted in highly accurate classification with a sensitivity and specificity of 1 when tested on the holdout test data set. On the other hand, no proteins were identified to correlate with non-germinal center B-cell like (non-GCB) or GCB subtypes to a significant degree after correction for multiple testing. However, functional analysis suggested that antigen binding is regulated when comparing non-GCB and GCB. Survival analysis based on protein quantitative values and clinical parameters identified multiple EV proteins as significantly correlated to survival. In conclusion, the plasma extracellular vesicle proteome identifies DLBCL cancer patients from healthy donors and contains potential EV protein markers for prediction of survival.<\/jats:p>","DOI":"10.3390\/ijms232113327","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T08:15:12Z","timestamp":1667376912000},"page":"13327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Extracellular Vesicles in Diffuse Large B Cell Lymphoma: Characterization and Diagnostic Potential"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2616","authenticated-orcid":false,"given":"Rune","family":"Matthiesen","sequence":"first","affiliation":[{"name":"Computational and Experimental Biology Group, NOVA Medical School-Research, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Gameiro","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia, Departament of Hematology, 1099-213 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-873X","authenticated-orcid":false,"given":"Andreia","family":"Henriques","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, NOVA Medical School-Research, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Bodo","sequence":"additional","affiliation":[{"name":"Champalimaud Physiology and Cancer Programme, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carolina Strano","family":"Moraes","sequence":"additional","affiliation":[{"name":"Champalimaud Physiology and Cancer Programme, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-6211","authenticated-orcid":false,"given":"Bruno","family":"Costa-Silva","sequence":"additional","affiliation":[{"name":"Champalimaud Physiology and Cancer Programme, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-1596","authenticated-orcid":false,"given":"Jos\u00e9","family":"Cabe\u00e7adas","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia, Departament of Hematology, 1099-213 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-2450","authenticated-orcid":false,"given":"Maria","family":"Gomes da Silva","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia, Departament of Hematology, 1099-213 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7763-3637","authenticated-orcid":false,"given":"Hans Christian","family":"Beck","sequence":"additional","affiliation":[{"name":"Centre for Clinical Proteomics, Department of Clinical Biochemistry, Odense University Hospital, DK-5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-1907","authenticated-orcid":false,"given":"Ana Sofia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, NOVA Medical School-Research, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1179\/102453312X13336169156014","article-title":"New developments in the management of diffuse large B-cell lymphoma","volume":"17","author":"Habermann","year":"2012","journal-title":"Hematology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1053\/j.seminhematol.2015.01.006","article-title":"The histological classification of diffuse large B-cell lymphomas","volume":"52","author":"Xie","year":"2015","journal-title":"Semin. 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