Jongmin Park, Jun Seok Park, Chen-Han Huang, Ala Jo, Kaitlyn Cook, Rui Wang, Hsing-Ying Lin, Jan Van Deun, Huiyan Li, Jouha Min, Lan Wang, Ghilsuk Yoon, Bob S Carter, Leonora Balaj, Gyu-Seog Choi, Cesar M Castro, Ralph Weissleder, Hakho Lee
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...
July 2021: Nature Biomedical Engineering