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HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.
Sun, Na; Zhang, Ceng; Lee, Yi-Te; Tran, Benjamin V; Wang, Jing; Kim, Hyoyong; Lee, Junseok; Zhang, Ryan Y; Wang, Jasmine J; Hu, Junhui; Zhang, Zhicheng; Alsudaney, Manaf S; Hou, Kuan-Chu; Tang, Hubert; Zhang, Tiffany X; Liang, Icy Y; Zhou, Ziang; Chen, Mengxiang; Yeh, Angela Hsiao-Jiun; Li, Wenyuan; Zhou, Xianghong Jasmine; Chang, Helena R; Han, Steven-Huy B; Sadeghi, Saeed; Finn, Richard S; Saab, Sammy; Busuttil, Ronald W; Noureddin, Mazen; Ayoub, Walid S; Kuo, Alexander; Sundaram, Vinay; Al-Ghaieb, Buraq; Palomique, Juvelyn; Kosari, Kambiz; Kim, Irene K; Todo, Tsuyoshi; Nissen, Nicholas N; Tomasi, Maria Lauda; You, Sungyong; Posadas, Edwin M; Wu, James X; Wadehra, Madhuri; Sim, Myung-Shin; Li, Yunfeng; Wang, Hanlin L; French, Samuel W; Lu, Shelly C; Wu, Lily; Pei, Renjun; Liang, Li.
Afiliação
  • Sun N; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Zhang C; Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics , University of Chinese Academy of Sciences, Chinese Academy of Sciences , Suzhou , People's Republic of China.
  • Lee YT; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Tran BV; Department of Pathology, Basic Medical College , Southern Medical University , Guangzhou , People's Republic of China.
  • Wang J; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Kim H; Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Lee J; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Zhang RY; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Wang JJ; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Hu J; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Zhang Z; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Alsudaney MS; Division of Medical Oncology, Department of Medicine , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Hou KC; Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Tang H; Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Zhang TX; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Liang IY; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Zhou Z; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Chen M; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Yeh AH; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Li W; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Zhou XJ; California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
  • Chang HR; Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Han SB; Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Sadeghi S; Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Finn RS; Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Saab S; Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Busuttil RW; Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Noureddin M; Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Ayoub WS; Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Kuo A; Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Sundaram V; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Al-Ghaieb B; Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Palomique J; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Kosari K; Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Kim IK; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Todo T; Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Nissen NN; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Tomasi ML; Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • You S; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Posadas EM; Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Wu JX; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Wadehra M; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Sim MS; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Li Y; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Wang HL; Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • French SW; Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Lu SC; Departments of Surgery and Biomedical Sciences , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Wu L; Division of Medical Oncology, Department of Medicine , Cedars-Sinai Medical Center , Los Angeles , California , USA.
  • Pei R; Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
  • Liang L; Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Hepatology ; 77(3): 774-788, 2023 03 01.
Article em En | MEDLINE | ID: mdl-35908246
ABSTRACT
BACKGROUND AND

AIMS:

The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND

RESULTS:

Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral 0.95; 95% CI, 0.90-1.00; nonviral 0.94; 95% CI, 0.88-0.99).

CONCLUSION:

HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Vesículas Extracelulares / Neoplasias Hepáticas Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Humans Idioma: En Revista: Hepatology Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Vesículas Extracelulares / Neoplasias Hepáticas Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Humans Idioma: En Revista: Hepatology Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos