HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

Humans Carcinoma, Hepatocellular / diagnosis Liver Neoplasms / diagnosis Biomarkers, Tumor / analysis Extracellular Vesicles / chemistry Membrane Proteins Electrocardiography Glypicans

Journal

Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946

Informations de publication

Date de publication:
01 03 2023
Historique:
received: 14 03 2022
accepted: 18 07 2022
pubmed: 1 8 2022
medline: 22 2 2023
entrez: 31 7 2022
Statut: ppublish

Résumé

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. 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). HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Sections du résumé

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.

Identifiants

DOI: 10.1002/hep.32692 PMID: 35908246 PMC: PMC9887095
pubmed: 35908246
pii: 01515467-202303000-00009
doi: 10.1002/hep.32692
pmc: PMC9887095
mid: NIHMS1845682
doi:

Substances chimiques

Biomarkers, Tumor 0
Membrane Proteins 0
GPC3 protein, human 0
Glypicans 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

774-788

Subventions

Organisme : NCI NIH HHS
ID : R01 CA218356
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA235340
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA255727
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA233452
Pays : United States
Organisme : NIBIB NIH HHS
ID : U01 EB026421
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA230705
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA143930
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA143931
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA198900
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA253651
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA246304
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA240887
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2023 American Association for the Study of Liver Diseases.

Références

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Auteurs

Na 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.
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.

Ceng Zhang (C)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Department of Pathology, Basic Medical College , Southern Medical University , Guangzhou , People's Republic of China.

Yi-Te 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.
ORCID: 0000-0002-8177-0407

Benjamin V Tran (BV)

Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Jing 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.
ORCID: 0000-0003-2751-9868

Hyoyong Kim (H)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Junseok 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.

Ryan Y 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.

Jasmine J 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.
Division of Medical Oncology, Department of Medicine , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Junhui Hu (J)

Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Zhicheng Zhang (Z)

Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Manaf S Alsudaney (MS)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Kuan-Chu Hou (KC)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Hubert Tang (H)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Tiffany X Zhang (TX)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Icy Y 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.

Ziang 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.

Mengxiang 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.

Angela Hsiao-Jiun Yeh (AH)

Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Wenyuan Li (W)

Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Xianghong Jasmine Zhou (XJ)

Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Helena R Chang (HR)

Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Steven-Huy B Han (SB)

Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Saeed Sadeghi (S)

Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Richard S Finn (RS)

Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Sammy Saab (S)

Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Ronald W Busuttil (RW)

Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
ORCID: 0000-0001-8157-1531

Mazen Noureddin (M)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Walid S Ayoub (WS)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Alexander Kuo (A)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Vinay Sundaram (V)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
ORCID: 0000-0002-1450-7756

Buraq Al-Ghaieb (B)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Juvelyn Palomique (J)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Kambiz Kosari (K)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Irene K Kim (IK)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Tsuyoshi Todo (T)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Nicholas N Nissen (NN)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Maria Lauda Tomasi (ML)

Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
ORCID: 0000-0001-8156-9052

Sungyong You (S)

Departments of Surgery and Biomedical Sciences , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Edwin M Posadas (EM)

Division of Medical Oncology, Department of Medicine , Cedars-Sinai Medical Center , Los Angeles , California , USA.

James X Wu (JX)

Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Madhuri Wadehra (M)

Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Myung-Shin Sim (MS)

Department of Medicine, Statistics Core, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Yunfeng Li (Y)

Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Hanlin L Wang (HL)

Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Samuel W French (SW)

Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.

Shelly C Lu (SC)

Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Samuel Oschin Comprehensive Cancer Institute , Cedars-Sinai Medical Center , Los Angeles , California , USA.

Lily Wu (L)

Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.

Renjun Pei (R)

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.

Li Liang (L)

Department of Pathology, Nanfang Hospital and Basic Medical College , Southern Medical University , Guangzhou , People's Republic of China.
Guangdong Province Key Laboratory of Molecular Tumor Pathology , Guangzhou , People's Republic of China.

Ju Dong Yang (JD)

Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Samuel Oschin Comprehensive Cancer Institute , Cedars-Sinai Medical Center , Los Angeles , California , USA.
ORCID: 0000-0001-7834-9825

Vatche G Agopian (VG)

Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Jonsson Comprehensive Cancer Center , University of California, Los Angeles , Los Angeles , California , USA.
ORCID: 0000-0003-0130-9838

Hsian-Rong Tseng (HR)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Jonsson Comprehensive Cancer Center , University of California, Los Angeles , Los Angeles , California , USA.

Yazhen Zhu (Y)

California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Jonsson Comprehensive Cancer Center , University of California, Los Angeles , Los Angeles , California , USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Vésicules extracellulaires › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Électrodiagnostic › Électrocardiographie › HCC EV ECG score: An extracellular...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › Glypicanes › HCC EV ECG score: An extracellular...