Proteomic landscape of extracellular vesicles for diffuse large b‐cell lymphoma subtyping

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 prote-ome and the whole‐cell proteome possess the capacity to separate cell lines into ABC and GCB sub-types. 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 endocyto-sis. 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.

Original languageEnglish
Article number11004
JournalInternational Journal of Molecular Sciences
Volume22
Issue number20
DOIs
Publication statusPublished - 1 Oct 2021

Keywords

  • Diffuse large B‐cell lymphoma
  • DLBCL
  • Exosomes
  • Extracellular vesicles
  • Mass spectrometry
  • Proteomics

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