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Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring

Author

Listed:
  • Na Sun

    (University of California
    University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Yi-Te Lee

    (University of California)

  • Ryan Y. Zhang

    (University of California)

  • Rueihung Kao

    (University of California)

  • Pai-Chi Teng

    (Cedars-Sinai Medical Center)

  • Yingying Yang

    (University of California)

  • Peng Yang

    (University of California)

  • Jasmine J. Wang

    (Cedars-Sinai Medical Center)

  • Matthew Smalley

    (University of California)

  • Pin-Jung Chen

    (University of California)

  • Minhyung Kim

    (Cedars-Sinai Medical Center)

  • Shih-Jie Chou

    (University of California)

  • Lirong Bao

    (University of California)

  • Jing Wang

    (University of California)

  • Xinyue Zhang

    (University of California)

  • Dongping Qi

    (University of California)

  • Juvelyn Palomique

    (Cedars-Sinai Medical Center)

  • Nicolas Nissen

    (Cedars-Sinai Medical Center)

  • Steven-Huy B. Han

    (University of California)

  • Saeed Sadeghi

    (University of California
    University of California)

  • Richard S. Finn

    (University of California
    University of California)

  • Sammy Saab

    (University of California)

  • Ronald W. Busuttil

    (University of California
    University of California)

  • Daniela Markovic

    (University of California)

  • David Elashoff

    (University of California)

  • Hsiao-hua Yu

    (Academia Sinica)

  • Huiying Li

    (University of California)

  • Anthony P. Heaney

    (University of California)

  • Edwin Posadas

    (Cedars-Sinai Medical Center)

  • Sungyong You

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Ju Dong Yang

    (Cedars-Sinai Medical Center
    Cedars Sinai Medical Center)

  • Renjun Pei

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Vatche G. Agopian

    (University of California
    University of California)

  • Hsian-Rong Tseng

    (University of California
    University of California)

  • Yazhen Zhu

    (University of California)

Abstract

We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).

Suggested Citation

  • Na Sun & Yi-Te Lee & Ryan Y. Zhang & Rueihung Kao & Pai-Chi Teng & Yingying Yang & Peng Yang & Jasmine J. Wang & Matthew Smalley & Pin-Jung Chen & Minhyung Kim & Shih-Jie Chou & Lirong Bao & Jing Wang, 2020. "Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18311-0
    DOI: 10.1038/s41467-020-18311-0
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