{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T03:50:01Z","timestamp":1776829801265,"version":"3.51.2"},"reference-count":62,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-TEC\/30087\/2017"],"award-info":[{"award-number":["PTDC\/BTM-TEC\/30087\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288\/1115 significantly differential expressed proteins from the whole-cell proteome and 228\/608 proteins from EVs (adjust p-value &lt; 0.05\/p-value &lt; 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.<\/jats:p>","DOI":"10.3390\/ijms222011004","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T06:38:41Z","timestamp":1634107121000},"page":"11004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-1907","authenticated-orcid":false,"given":"Ana Sofia","family":"Carvalho","sequence":"first","affiliation":[{"name":"Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8481-9416","authenticated-orcid":false,"given":"Henrique","family":"Baeta","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-873X","authenticated-orcid":false,"given":"Andreia F. A.","family":"Henriques","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6508-8707","authenticated-orcid":false,"given":"Mostafa","family":"Ejtehadifar","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"given":"Erin M.","family":"Tranfield","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6067-8794","authenticated-orcid":false,"given":"Ana Laura","family":"Sousa","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal"}]},{"given":"Ana","family":"Farinho","sequence":"additional","affiliation":[{"name":"iNOVA4Health\u2014Advancing Precision Medicine, CEDOC\u2014Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5932-6211","authenticated-orcid":false,"given":"Bruno Costa","family":"Silva","sequence":"additional","affiliation":[{"name":"Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-1596","authenticated-orcid":false,"given":"Jos\u00e9","family":"Cabe\u00e7adas","sequence":"additional","affiliation":[{"name":"Pathology Department, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-7050","authenticated-orcid":false,"given":"Paula","family":"Gameiro","sequence":"additional","affiliation":[{"name":"Haematology Unit, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-2450","authenticated-orcid":false,"given":"Maria Gomes da","family":"Silva","sequence":"additional","affiliation":[{"name":"Haematology Unit, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, Portugal"}]},{"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 and Pharmacology, Odense University Hospital, DK-5000 Odense, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2616","authenticated-orcid":false,"given":"Rune","family":"Matthiesen","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1056\/NEJMoa0802885","article-title":"Stromal gene signatures in large-B-cell lymphomas","volume":"359","author":"Lenz","year":"2008","journal-title":"N. 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