Extracellular Vesicles in Diffuse Large B Cell Lymphoma: Characterization and Diagnostic Potential

Abstract

Diffuse large B cell lymphoma (DLBCL) is an aggressive B cell lymphoma characterized by a heterogeneous behavior and in need of more accurate biological characterization monitoring and prognostic tools. Extracellular vesicles are secreted by all cell types and are currently established to some extent as representatives of the cell of origin. The present study characterized and evaluated the diagnostic and prognostic potential of plasma extracellular vesicles (EVs) proteome in DLBCL by using state-of-the-art mass spectrometry. The EV proteome is strongly affected by DLBCL status, with multiple proteins uniquely identified in the plasma of DLBCL. A proof-of-concept classifier resulted in highly accurate classification with a sensitivity and specificity of 1 when tested on the holdout test data set. On the other hand, no proteins were identified to correlate with non-germinal center B-cell like (non-GCB) or GCB subtypes to a significant degree after correction for multiple testing. However, functional analysis suggested that antigen binding is regulated when comparing non-GCB and GCB. Survival analysis based on protein quantitative values and clinical parameters identified multiple EV proteins as significantly correlated to survival. In conclusion, the plasma extracellular vesicle proteome identifies DLBCL cancer patients from healthy donors and contains potential EV protein markers for prediction of survival.

Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in a cross-sectional study

“…MS-based proteome data based on urinary sEV preparations from 100 patients were quality checked for exosome markers (Figure 2A). The urinary sEVs from the current study had the highest expression of established small EV markers compared to previous studies based on sEV samples from other sources, such as cell lines [11][12][13] , lung uids 14 , and blood plasma 15 . Urinary sEVs were devoid of microsomes or large EVs protein markers.…”

Proteomic Research of Extracellular Vesicles in Clinical Biofluid

“…Chang et al [ 43 ] found an EV protein signature (six proteins) derived from the serum of colorectal cancer patients where APOF and CFB are linked to clathrin-mediated endocytosis signaling, and the complement system is considered crucial for the development of tumorigenesis. Matthiesen et al [ 44 ] collected EVs from plasma and performed proteomic profiles to distinguish diffuse large B cell lymphoma cancer patients and proposed the use of EV protein indicators to predict prospective survival. By virtue of quantitative proteomics and further verification through ELISA and immunoblot, Hou et al [ 45 ] found that Stratifin, a member of the 14-3-3 protein family generated from the serum EVs of colorectal cancer patients, is a biomarker to predict prognosis.…”

PBMC‐derived extracellular vesicles in a smoking‐related inflammatory disease model

“…Proteins not present in EV samples were listed as not detected. Of the proteins detected, 25 have commonly been reported as associated with EVs [42][43][44], two proteins usually associated with being part of lysosomes and/or EVs [45], and one protein associated with peroxisomes and/or EVs [46].…”