Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping

• Published in: International journal of molecular sciences Vol. 22; no. 20; p. 11004
• Main Authors: 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, Silva, Maria Gomes da, Beck, Hans Christian, Matthiesen, Rune
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-10-2021; MDPI
• Subjects: B-cell lymphoma; B-cell receptor; B-Lymphocytes - metabolism; Biological activity; Biomarkers; Biopsy; Cell Line, Tumor; Combinatorial analysis; diffuse large B-cell lymphoma; DLBCL; Endocytosis; Enrichment; ErbB protein; exosomes; Extracellular vesicles; Extracellular Vesicles - metabolism; Fc receptors; Functional analysis; Gene expression; Germinal Center - cytology; Germinal Center - metabolism; Humans; Immunosuppressive agents; Intracellular signalling; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Mass Spectrometry; Mass spectroscopy; Medical prognosis; Ontology; Phagocytosis; Proteins; Proteome - analysis; Proteomes; Proteomics; Proteomics - methods; Quality assessment; Quality control; Quality standards; Response functions; Therapeutic targets; Vesicles; mass spectrometry; DLBCL; extracellular vesicles; diffuse large B-cell lymphoma; proteomics; exosomes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222011004

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
-value < 0.05/
-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.