Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.976407/full |
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| author | Jisu Lee Hyun Sik Park Seung Ro Han Seung Ro Han Yun Hee Kang Yun Hee Kang Ji Young Mun Dong Wook Shin Hyun-Woo Oh Yoon-Kyoung Cho Yoon-Kyoung Cho Myung-Shin Lee Myung-Shin Lee Jinsung Park Jinsung Park |
| author_facet | Jisu Lee Hyun Sik Park Seung Ro Han Seung Ro Han Yun Hee Kang Yun Hee Kang Ji Young Mun Dong Wook Shin Hyun-Woo Oh Yoon-Kyoung Cho Yoon-Kyoung Cho Myung-Shin Lee Myung-Shin Lee Jinsung Park Jinsung Park |
| author_sort | Jisu Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:41:12Z |
| format | Article |
| id | doaj.art-870aff5746be44d78c1f9975daa19dc8 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T21:41:12Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-870aff5746be44d78c1f9975daa19dc82022-12-22T03:15:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.976407976407Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesiclesJisu Lee0Hyun Sik Park1Seung Ro Han2Seung Ro Han3Yun Hee Kang4Yun Hee Kang5Ji Young Mun6Dong Wook Shin7Hyun-Woo Oh8Yoon-Kyoung Cho9Yoon-Kyoung Cho10Myung-Shin Lee11Myung-Shin Lee12Jinsung Park13Jinsung Park14Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South KoreaDepartment of Urology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, South KoreaDepartment of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South KoreaEulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, South KoreaDepartment of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South KoreaEulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, South KoreaNeural Circuit Research Group, Korea Brain Research Institute, Daegu, South KoreaDepartment of Family Medicine/Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South KoreaCore Facility Management Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South KoreaCenter for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan, South KoreaDepartment of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South KoreaEulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, South KoreaDepartment of Urology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, South KoreaDepartment of Urology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu-si, South KoreaExtracellular 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.976407/fullalpha-2-macroglobulinbladder cancerextracellular vesicles (EVs)urinebiomarker |
| spellingShingle | Jisu Lee Hyun Sik Park Seung Ro Han Seung Ro Han Yun Hee Kang Yun Hee Kang Ji Young Mun Dong Wook Shin Hyun-Woo Oh Yoon-Kyoung Cho Yoon-Kyoung Cho Myung-Shin Lee Myung-Shin Lee Jinsung Park Jinsung Park Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles Frontiers in Oncology alpha-2-macroglobulin bladder cancer extracellular vesicles (EVs) urine biomarker |
| title | Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles |
| title_full | Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles |
| title_fullStr | Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles |
| title_full_unstemmed | Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles |
| title_short | Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles |
| title_sort | alpha 2 macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles |
| topic | alpha-2-macroglobulin bladder cancer extracellular vesicles (EVs) urine biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.976407/full |
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