ArticleHepatology (Baltimore, Md.)2023
HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.
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Article in Hepatology (Baltimore, Md.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62citing papers in PubMed
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62 citing papers in PubMed, 85 citations in OpenAlex.
- Tissue-Specific Isolation of Hepatocyte Extracellular Vesicles From Human Plasma Enables Tissue-Resolved Proteomic and miRNA Profiling.Journal of extracellular vesicles · 2026Article
- Multi-Target HCC Blood Test Demonstrates Consistent Performance Across Subgroups of Patients with Chronic Liver Disease.Cancers · 2026Article
- Non-Invasive Assessment of Microvascular Invasion Risk in Hepatocellular Carcinoma Using Liquid Biopsy: Translational Insights and Clinical Implications.Diagnostics (Basel, Switzerland) · 2026Review
- Methylation plus alpha-fetoprotein blood test for early detection of HCC in at-risk populations.Hepatology communications · 2026Article
- Bioorthogonal Click Chemistry-Enabled Enrichment of Extracellular Vesicles for Integrated Molecular and Functional Liquid Biopsy§.Accounts of chemical research · 2026Article
- Extracellular vesicle and particle biomarkers in cancer: a machine learning blueprint for liquid biopsy.Journal of nanobiotechnology · 2026Review
- Detection of Extracellular Vesicles with Colocalized Surface Markers via a Capture-Release-Capture Strategy for Treatment Monitoring in Ewing Sarcoma.Advanced healthcare materials · 2026Article
- Advances in the mechanisms of extracellular vesicles and circulating tumor cells in hepatocellular carcinoma metastasis (Review).Molecular medicine reports · 2026Review
- Developing blood extracellular vesicle protein biomarkers for hepatocellular carcinoma: mechanisms, methods, and translation.Journal of nanobiotechnology · 2026Review
- Quantification of DNA Methylation for Diagnosis and Monitoring of Hepatocellular Carcinoma.Journal of the American College of Surgeons · 2026Article
- Proteomic Profiling of Human Extracellular Vesicles Reveals Diagnostic Biomarkers for Colon Adenocarcinoma.Journal of extracellular vesicles · 2026Article
- Immune-modified exosome vaccine loaded with liver cancer epitope peptides induces potent and specific antitumor immunity.Journal of nanobiotechnology · 2026Article
- Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy.Research square · 2026Article
- Biomarkers for the Diagnosis of Cirrhosis and Cirrhosis-Related Complications.Gastroenterology clinics of North America · 2026Review
- Liquid biopsies in precision oncology for older adults with cancer.NPJ precision oncology · 2026Review
- Tumor Extracellular Vesicle Digital Scoring Assays for Cancer Detection and Monitoring.Precision chemistry · 2025Review
- What we missed then, AI sees now: Revisiting legacy large extracellular vesicle data to reveal synergistic biomarkers for liver cancer screening.JHEP reports : innovation in hepatology · 2025Article
- Noninvasive Assessment of Protease Activity in Osteosarcoma via Click Chemistry-Mediated Enrichment of Extracellular Vesicles.Advanced functional materials · 2025Article
- Serum Proteomic Profile Based on the TGF-β Pathway Stratifies Risk of Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care.Cancers · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
54 authors at 5 institutions in 2 countries.
Na SunCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Ceng ZhangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Yi-Te LeeCalifornia 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 TranDepartment of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Jing WangCalifornia 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 KimCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Junseok LeeCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Ryan Y ZhangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Jasmine J WangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Junhui HuDepartment of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Zhicheng ZhangDepartment of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Manaf S AlsudaneyComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Kuan-Chu HouCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Hubert TangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Tiffany X ZhangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Icy Y LiangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Ziang ZhouCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Mengxiang ChenCalifornia 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 YehDepartment of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Wenyuan LiDepartment 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 ZhouDepartment 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 ChangDepartment of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Steven-Huy B HanDepartment of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Saeed SadeghiDepartment of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Richard S FinnDepartment of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Sammy SaabDepartment of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Ronald W BusuttilDepartment of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.ORCID 0000-0001-8157-1531
Mazen NoureddinComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Walid S AyoubComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Alexander KuoComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Vinay SundaramComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.ORCID 0000-0002-1450-7756
Buraq Al-GhaiebComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Juvelyn PalomiqueComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Kambiz KosariComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Irene K KimComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Tsuyoshi TodoComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Nicholas N NissenComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Maria Lauda TomasiKarsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.ORCID 0000-0001-8156-9052
Sungyong YouDepartments of Surgery and Biomedical Sciences , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Edwin M PosadasDivision of Medical Oncology, Department of Medicine , Cedars-Sinai Medical Center , Los Angeles , California , USA.
James X WuDepartment of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Madhuri WadehraDepartment 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 SimDepartment of Medicine, Statistics Core, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
Yunfeng LiDepartment 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 WangDepartment 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 FrenchDepartment 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 LuKarsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
Lily WuDepartment of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Renjun PeiKey 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 LiangDepartment of Pathology, Nanfang Hospital and Basic Medical College , Southern Medical University , Guangzhou , People's Republic of China.
Ju Dong YangComprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.ORCID 0000-0001-7834-9825
Vatche G AgopianDepartment of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.ORCID 0000-0003-0130-9838
Hsian-Rong TsengCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
Yazhen ZhuCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
University of California, Los Angeles · USCedars-Sinai Medical Center · USCalifornia NanoSystems Institute · USKey Laboratory of Guangdong Province · CNSuzhou Institute of Nano-tech and Nano-bionics · CN
Funding
Supporting African American Churches to Promote Cancer ScreeningU54CA143931 · NCI · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI VADGAMA, JAYDUTT V. · 2009 to 2022
$19.7MThe paradoxical roles of beta hydroxy butyrate in the liver pro-metastatic nicheP01CA233452 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LU, SHELLY CHI-LOO · 2020 to 2024
$9.5MTraining and Mentoring ProgramsU54CA143930 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PIETRAS, RICHARD JOSEPH · 2009 to 2020
$7.5MThe UCLA Center in Early Detection of Liver CancerU01CA230705 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Vatche Agopian, Samuel Wheeler French · 2018 to 2026
$6.6MNon-Invasive Prenatal Diagnostics Based on Circulating TrophoblastsU01EB026421 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PISARSKA, MARGARETA, TSENG, HSIAN-RONG · 2019 to 2023
$4.0MHCC EV Digital Scoring Assay for assessing treatment response in HCC patientsR01CA253651 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TSENG, HSIAN-RONG, ZHU, YAZHEN · 2020 to 2024
$3.3MExtracellular Vesicle-Based Digital Scoring Assay for Detecting Early-stage Hepatocellular CarcinomaR01CA255727 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHU, YAZHEN · 2021 to 2025
$3.2MA blood test to identify prostate cancer patients at risk for visceral metastasisR01CA218356 · NCI · CEDARS-SINAI MEDICAL CENTER · PI POSADAS, EDWIN MELENCIO, TSENG, HSIAN-RONG · 2017 to 2021
$3.0MIntegrated analysis of HCC CTCs for Liver Transplant Candidate SelectionR01CA246304 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2020 to 2024
$2.8MThermoresponsive NanoVelcro CTC Purification System for Prostate Cancer ProfilingU01CA198900 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI POSADAS, EDWIN MELENCIO, TSENG, HSIAN-RONG · 2015 to 2019
$2.4MClick Chemistry-Mediated Microfluidic Sorting for HCC CTCsR21CA235340 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2019 to 2021
$543kBiomimetic NanoVilli Chips for Extracellular Vesicles in Hepatocellular CarcinomaR21CA240887 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2020 to 2021
$419kNCI NIH HHS P01 CA233452NCI NIH HHS R01 CA218356NCI NIH HHS R01 CA246304NCI NIH HHS R01 CA253651NCI NIH HHS R01 CA255727NCI NIH HHS R21 CA235340NCI NIH HHS R21 CA240887NCI NIH HHS U01 CA198900NCI NIH HHS U01 CA230705NCI NIH HHS U54 CA143930NCI NIH HHS U54 CA143931NIBIB NIH HHS U01 EB026421
Abstract
BACKGROUND AND
aimsThe 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
resultsTissue 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).
conclusionHCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.
Indexed as
Carcinoma, HepatocellularExtracellular VesiclesLiver NeoplasmsBiomarkers, TumorElectrocardiographyGlypicansHumansMembrane ProteinsBiomarkers, TumorGlypicansGPC3 protein, humanMembrane Proteins
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