Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping
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 su...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/20/11004 |
| _version_ | 1797514395706720256 |
|---|---|
| author | Ana Sofia Carvalho Henrique Baeta Andreia F. A. Henriques Mostafa Ejtehadifar Erin M. Tranfield Ana Laura Sousa Ana Farinho Bruno Costa Silva José Cabeçadas Paula Gameiro Maria Gomes da Silva Hans Christian Beck Rune Matthiesen |
| author_facet | Ana Sofia Carvalho Henrique Baeta Andreia F. A. Henriques Mostafa Ejtehadifar Erin M. Tranfield Ana Laura Sousa Ana Farinho Bruno Costa Silva José Cabeçadas Paula Gameiro Maria Gomes da Silva Hans Christian Beck Rune Matthiesen |
| author_sort | Ana Sofia Carvalho |
| collection | DOAJ |
| description | 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 <i>p</i>-value < 0.05/<i>p</i>-value < 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. |
| first_indexed | 2024-03-10T06:31:01Z |
| format | Article |
| id | doaj.art-b0f431b7569b4882abde65ab0e3a2641 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:31:01Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b0f431b7569b4882abde65ab0e3a26412023-11-22T18:32:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201100410.3390/ijms222011004Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma SubtypingAna Sofia Carvalho0Henrique Baeta1Andreia F. A. Henriques2Mostafa Ejtehadifar3Erin M. Tranfield4Ana Laura Sousa5Ana Farinho6Bruno Costa Silva7José Cabeçadas8Paula Gameiro9Maria Gomes da Silva10Hans Christian Beck11Rune Matthiesen12Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, PortugalComputational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, PortugalComputational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, PortugalComputational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, PortugalElectron Microscopy Facility, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, PortugalElectron Microscopy Facility, Instituto Gulbenkian de Ciência, 2780-156 Oeiras, PortugaliNOVA4Health—Advancing Precision Medicine, CEDOC—Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, PortugalSystems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisbon, PortugalPathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, PortugalHaematology Unit, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, PortugalHaematology Unit, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisbon, PortugalCentre for Clinical Proteomics, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, DK-5000 Odense, DenmarkComputational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, PortugalThe 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 <i>p</i>-value < 0.05/<i>p</i>-value < 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.https://www.mdpi.com/1422-0067/22/20/11004extracellular vesiclesexosomesDLBCLdiffuse large B-cell lymphomaproteomicsmass spectrometry |
| spellingShingle | Ana Sofia Carvalho Henrique Baeta Andreia F. A. Henriques Mostafa Ejtehadifar Erin M. Tranfield Ana Laura Sousa Ana Farinho Bruno Costa Silva José Cabeçadas Paula Gameiro Maria Gomes da Silva Hans Christian Beck Rune Matthiesen Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping International Journal of Molecular Sciences extracellular vesicles exosomes DLBCL diffuse large B-cell lymphoma proteomics mass spectrometry |
| title | Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping |
| title_full | Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping |
| title_fullStr | Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping |
| title_full_unstemmed | Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping |
| title_short | Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping |
| title_sort | proteomic landscape of extracellular vesicles for diffuse large b cell lymphoma subtyping |
| topic | extracellular vesicles exosomes DLBCL diffuse large B-cell lymphoma proteomics mass spectrometry |
| url | https://www.mdpi.com/1422-0067/22/20/11004 |
| work_keys_str_mv | AT anasofiacarvalho proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT henriquebaeta proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT andreiafahenriques proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT mostafaejtehadifar proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT erinmtranfield proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT analaurasousa proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT anafarinho proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT brunocostasilva proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT josecabecadas proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT paulagameiro proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT mariagomesdasilva proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT hanschristianbeck proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping AT runematthiesen proteomiclandscapeofextracellularvesiclesfordiffuselargebcelllymphomasubtyping |