An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma.

Adolescent Adult Aged Aged, 80 and over Antibodies, Immobilized / chemistry Area Under Curve Biomarkers, Tumor / blood Colorectal Neoplasms / diagnosis Disease-Free Survival Electrochemical Techniques / methods Epithelial Cell Adhesion Molecule / blood Extracellular Vesicles / immunology Female Humans Kaplan-Meier Estimate Longitudinal Studies Male Middle Aged Prognosis ROC Curve Recurrence Young Adult

Journal

Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896

Informations de publication

Date de publication:
07 2021
Historique:
received: 21 11 2019
accepted: 18 05 2021
pubmed: 30 6 2021
medline: 7 9 2021
entrez: 29 6 2021
Statut: ppublish

Résumé

Assays for cancer diagnosis via the analysis of biomarkers on circulating extracellular vesicles (EVs) typically have lengthy sample workups, limited throughput or insufficient sensitivity, or do not use clinically validated biomarkers. Here we report the development and performance of a 96-well assay that integrates the enrichment of EVs by antibody-coated magnetic beads and the electrochemical detection, in less than one hour of total assay time, of EV-bound proteins after enzymatic amplification. By using the assay with a combination of antibodies for clinically relevant tumour biomarkers (EGFR, EpCAM, CD24 and GPA33) of colorectal cancer (CRC), we classified plasma samples from 102 patients with CRC and 40 non-CRC controls with accuracies of more than 96%, prospectively assessed a cohort of 90 patients, for whom the burden of tumour EVs was predictive of five-year disease-free survival, and longitudinally analysed plasma from 11 patients, for whom the EV burden declined after surgery and increased on relapse. Rapid assays for the detection of combinations of tumour biomarkers in plasma EVs may aid cancer detection and patient monitoring.

Identifiants

DOI: 10.1038/s41551-021-00752-7 PMID: 34183802 PMC: PMC8437135
pubmed: 34183802
doi: 10.1038/s41551-021-00752-7
pii: 10.1038/s41551-021-00752-7
pmc: PMC8437135
mid: NIHMS1706321
doi:

Substances chimiques

Antibodies, Immobilized 0
Biomarkers, Tumor 0
EPCAM protein, human 0
Epithelial Cell Adhesion Molecule 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

678-689

Subventions

Organisme : NCATS NIH HHS
ID : UH3 TR000931
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA069246
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229777
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237500
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239078
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA205322
Pays : United States
Organisme : NCATS NIH HHS
ID : UH2 TR000931
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA230697
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA049577
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204019
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113156
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA233360
Pays : United States

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Jongmin Park (J)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Chemistry, Kangwon National University, Chuncheon, Korea.
ORCID: 0000-0001-8338-9346

Jun Seok Park (JS)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.

Chen-Han Huang (CH)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan.

Ala Jo (A)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Kaitlyn Cook (K)

Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
ORCID: 0000-0003-3794-3312

Rui Wang (R)

Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-5007-193X

Hsing-Ying Lin (HY)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Jan Van Deun (J)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Huiyan Li (H)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Jouha Min (J)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-6737-7254

Lan Wang (L)

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Ghilsuk Yoon (G)

Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea.

Bob S Carter (BS)

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Leonora Balaj (L)

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-0931-9715

Gyu-Seog Choi (GS)

Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.

Cesar M Castro (CM)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Ralph Weissleder (R)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. rweissleder@mgh.harvard.edu.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. rweissleder@mgh.harvard.edu.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA. rweissleder@mgh.harvard.edu.
ORCID: 0000-0003-0828-4143

Hakho Lee (H)

Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. hlee@mgh.harvard.edu.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. hlee@mgh.harvard.edu.
ORCID: 0000-0002-0087-0909

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