Author(s):
Ferreira, Bruna Velosa ; Carneiro, Emilie Arnault ; Pestana, Carolina ; Barahona, Filipa ; Caetano, Joana ; Lopes, Raquel ; Lúcio, Paulo ; Neves, Manuel ; Beck, Hans Christian ; Carvalho, Ana Sofia ; Matthiesen, Rune ; Costa-Silva, Bruno ; João, Cristina
Date: 2022
Persistent ID: http://hdl.handle.net/10362/142168
Origin: Repositório Institucional da UNL
Subject(s): biomarkers; extracellular vesicles (EV); liquid biopsy; multiple myeloma; protein; Oncology; Cancer Research; SDG 3 - Good Health and Well-being
Description
Funding Information: This research was funded by the Champalimaud Foundation; by the Fundação para a Ciência e Tecnologia – FCT (Research Grant PTDC/MEC-HEM/30315/2017) and by Sociedade Portuguesa de Hematologia -SPH (Initiation to Investigation Grant 2018).
Multiple myeloma (MM) is a hematological malignancy of clonal antibody–secreting plasma cells (PCs). MM diagnosis and risk stratification rely on bone marrow (BM) biopsy, an invasive procedure prone to sample bias. Liquid biopsies, such as extracellular vesicles (EV) in peripheral blood (PB), hold promise as new minimally invasive tools. Real-world studies analyzing patient-derived EV proteome are rare. Here, we characterized a small EV protein content from PB and BM samples in a cohort of 102 monoclonal gammopathies patients routinely followed in the clinic and 223 PB and 111 BM samples were included. We investigated whether EV protein and particle concentration could predict an MM patient prognosis. We found that a high EV protein/particle ratio, or EV cargo >0.6 µg/108 particles, is related to poorer survival and immune dysfunction. These results were supported at the protein level by mass spectrometry. We report a set of PB EV-proteins (PDIA3, C4BPA, BTN1A1, and TNFSF13) with a new biomarker potential for myeloma patient outcomes. The high proteomic similarity between PB and BM matched pairs supports the use of circulating EV as a counterpart of the BM EV proteome. Overall, we found that the EV protein content is related to patient outcomes, such as survival, immune dysfunction, and possibly treatment response.
