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Challenges and Opportunities in State-of-the-Art Proteomics Analysis for Biomarker Development From Plasma Extracellular Vesicles
Journal article   Open access   Peer reviewed

Challenges and Opportunities in State-of-the-Art Proteomics Analysis for Biomarker Development From Plasma Extracellular Vesicles

Panshak P. Dakup, Ivo Diaz Ludovico, Youngki You, Chaitra Rao, Javier Flores, Lisa M. Bramer, Marian Rewers, Bobbie-Jo M. Webb-Robertson, Thomas O. Metz, Raghavendra G. Mirmira, …
Proteomics (Weinheim), Vol.26(2-3), pp.9-20
02/2026
DOI: 10.1002/pmic.70036
PMCID: PMC12604859
PMID: 40955644
url
https://doi.org/10.1002/pmic.70036View
Published (Version of record) Open Access

Abstract

Extracellular vesicles (EVs) are membrane-bound particles secreted by cells, playing crucial roles in intercellular communication. The composition of EVs can undergo changes in response to stress and disease conditions, making them excellent biomarker candidates. However, extracting protein information from EVs can be challenging due to their low abundance in complex biofluids and copurification with contaminant proteins and particles. Techniques to enrich EVs have their strengths and limitations, without one being able to purify EVs to complete homogeneity. This can lead to compromised recovery rates and increased complexity, making data interpretation difficult. In this viewpoint article, we explore the concept that better characterization of EV composition, followed by quantification of EV proteins in complex samples, might be a more viable route for biomarker development. Mass spectrometers can provide reproducible deep coverage of the EV proteome, despite sample impurities. This paradigm shift presents opportunities to integrate advanced bioinformatics tools to refine the EV proteome landscape, identify novel biomarkers, and streamline validation processes in biomarker development. By focusing on leveraging technology rather than achieving absolute purity, this approach can transform current practices and open opportunities for robust biomarker discovery. Herein, we highlight not only such opportunities but also challenges to implement this concept.
Biochemical Research Methods Biochemistry & Molecular Biology Life Sciences & Biomedicine Science & Technology

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