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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536203/ https://www.ncbi.nlm.nih.gov/pubmed/34681663 http://dx.doi.org/10.3390/ijms222011004 |
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author | Carvalho, Ana Sofia Baeta, Henrique Henriques, Andreia F. A. Ejtehadifar, Mostafa Tranfield, Erin M. Sousa, Ana Laura Farinho, Ana Silva, Bruno Costa Cabeçadas, José Gameiro, Paula da Silva, Maria Gomes Beck, Hans Christian Matthiesen, Rune |
author_facet | Carvalho, Ana Sofia Baeta, Henrique Henriques, Andreia F. A. Ejtehadifar, Mostafa Tranfield, Erin M. Sousa, Ana Laura Farinho, Ana Silva, Bruno Costa Cabeçadas, José Gameiro, Paula da Silva, Maria Gomes Beck, Hans Christian Matthiesen, Rune |
author_sort | Carvalho, Ana Sofia |
collection | PubMed |
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 p-value < 0.05/p-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. |
format | Online Article Text |
id | pubmed-8536203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85362032021-10-23 Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping Carvalho, Ana Sofia Baeta, Henrique Henriques, Andreia F. A. Ejtehadifar, Mostafa Tranfield, Erin M. Sousa, Ana Laura Farinho, Ana Silva, Bruno Costa Cabeçadas, José Gameiro, Paula da Silva, Maria Gomes Beck, Hans Christian Matthiesen, Rune Int J Mol Sci Article 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 < 0.05/p-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. MDPI 2021-10-12 /pmc/articles/PMC8536203/ /pubmed/34681663 http://dx.doi.org/10.3390/ijms222011004 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Carvalho, Ana Sofia Baeta, Henrique Henriques, Andreia F. A. Ejtehadifar, Mostafa Tranfield, Erin M. Sousa, Ana Laura Farinho, Ana Silva, Bruno Costa Cabeçadas, José Gameiro, Paula da Silva, Maria Gomes Beck, Hans Christian Matthiesen, Rune Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536203/ https://www.ncbi.nlm.nih.gov/pubmed/34681663 http://dx.doi.org/10.3390/ijms222011004 |
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