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Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.
Sun, Na; Lee, Yi-Te; Zhang, Ryan Y; Kao, Rueihung; Teng, Pai-Chi; Yang, Yingying; Yang, Peng; Wang, Jasmine J; Smalley, Matthew; Chen, Pin-Jung; Kim, Minhyung; Chou, Shih-Jie; Bao, Lirong; Wang, Jing; Zhang, Xinyue; Qi, Dongping; Palomique, Juvelyn; Nissen, Nicolas; Han, Steven-Huy B; Sadeghi, Saeed; Finn, Richard S; Saab, Sammy; Busuttil, Ronald W; Markovic, Daniela; Elashoff, David; Yu, Hsiao-Hua; Li, Huiying; Heaney, Anthony P; Posadas, Edwin; You, Sungyong; Yang, Ju Dong; Pei, Renjun; Agopian, Vatche G; Tseng, Hsian-Rong; Zhu, Yazhen.
Afiliação
  • Sun N; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Lee YT; Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 215123, Suzhou, P.R. China.
  • Zhang RY; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Kao R; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Teng PC; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Yang Y; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Yang P; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Wang JJ; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Smalley M; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Chen PJ; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Kim M; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Chou SJ; Division of Cancer Biology and Therapeutics, Departments of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Bao L; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Wang J; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Zhang X; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Qi D; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Palomique J; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Nissen N; Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Han SB; Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Sadeghi S; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Finn RS; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Saab S; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Busuttil RW; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Markovic D; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Elashoff D; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Yu HH; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Li H; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, 90095, USA.
  • Heaney AP; Department of Medicine, Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Posadas E; Department of Medicine, Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • You S; Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, 11529, Taipei, Taiwan.
  • Yang JD; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
  • Pei R; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Agopian VG; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Tseng HR; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Zhu Y; Division of Cancer Biology and Therapeutics, Departments of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Nat Commun ; 11(1): 4489, 2020 09 07.
Article em En | MEDLINE | ID: mdl-32895384
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%).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Carcinoma Hepatocelular / Detecção Precoce de Câncer / Vesículas Extracelulares / Neoplasias Hepáticas Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Carcinoma Hepatocelular / Detecção Precoce de Câncer / Vesículas Extracelulares / Neoplasias Hepáticas Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos