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Cho, Yoon-Kyoung
FRUITS Lab.
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Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles

Author(s)
Lee, JisuPark, Hyun SikHan, Seung RoKang, Yun HeeMun, Ji YoungShin, Dong WookOh, Hyun-WooCho, Yoon-KyoungLee, Myung-ShinPark, Jinsung
Issued Date
2022-09
DOI
10.3389/fonc.2022.976407
URI
https://scholarworks.unist.ac.kr/handle/201301/62196
Citation
FRONTIERS IN ONCOLOGY, v.12, pp.976407
Abstract
Extracellular vesicles (EVs) derived from urine are promising tools for the diagnosis of urogenital cancers. Urinary EVs (uEVs) are considered potential biomarkers for bladder cancer (BC) because urine is in direct contact with the BC tumor microenvironment and thus reflects the current state of the disease. However, challenges associated with the effective isolation and analysis of uEVs complicate the clinical detection of uEV-associated protein biomarkers. Herein, we identified uEV-derived alpha-2-macroglobulin (a2M) as a novel diagnostic biomarker for BC through comparative analysis of uEVs obtained from patients with BC pre- and post-operation using an antibody array. Furthermore, enzyme-linked immunosorbent assay of uEVs isolated from patients with BC (n=60) and non-cancer control subjects (n=23) validated the significant upregulation of a2M expression in patient uEVs (p<0.0001). There was no significant difference in whole urine a2M levels between patients with BC and controls (p=0.317). We observed that compared to classical differential centrifugation, ExoDisc, a centrifugal microfluidic tangential flow filtration device, was a significantly more effective separation method for uEV protein analysis. We expect that our approach for EV analysis will provide an efficient route for the identification of clinically meaningful uEV-based biomarkers for cancer diagnosis.
Publisher
FRONTIERS MEDIA SA
ISSN
2234-943X
Keyword (Author)
alpha-2-macroglobulinbladder cancerextracellular vesicles (EVs)urinebiomarker
Keyword
EXOSOMESIDENTIFICATIONCYSTOSCOPYMECHANISMSPROSTATECELLS

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