Authors
Ye Zhang, Yitong Zhu, Yu Zhang, Shijin Peng, Diheng Wu, Wenbin Li, Tingting Ji, Siting Chen, Yuanhong Lin, Huihong Yang, Yuhang Guo, Bo Li, Chunchen Liu, Bo Situ, Xiaohui Yan, Lei Zheng
Published in
Science advances. Volume 12. Issue 34. Pages eaef8133. Aug 21, 2026. Epub Aug 21, 2026.
Abstract
Extracellular vesicle-associated microRNAs (EV-miRNAs) hold promise for liquid biopsy, but their clinical utility is hindered by EV heterogeneity. Here, we report DEEPER, a DNA-encoded orthogonal recognition platform for selective barcoding of tumor-derived EV subpopulations and in situ miRNA profiling. DEEPER uses four aptamers targeting Cluster of Differentiation 44 (CD44), Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and Programmed Death-Ligand 1(PD-L1) to generate orthogonal barcodes that distinguish 15 EV subpopulations. Barcoded EVs then undergo targeted membrane fusion with liposome probes, enabling sensitive in situ analysis of subpopulation-specific miRNAs. In a 60-sample cohort of patients with gastric cancer (GC) and healthy donors (HDs), DEEPER identified a high-performing signature, GC-EV miRNA Prime, comprising EGFR+, EGFR+HER2+, and EGFR+HER2+CD44+ EVs, which achieved 98.3% diagnostic accuracy. The same profiling framework also assessed tumor invasiveness with 95.5% accuracy. Mechanistic studies further showed that these EV-miRNAs contribute to tumor progression. In summary, DEEPER not only confirmed the clinical application value of EV-miRNA-based liquid biopsy but also provided unique insights through the EV subpopulations into the mechanisms driving cancer development.
PMID:
42627892
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.
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