Observational studyNature communications2020
Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.
Open access · goldAbstract readObservational StudyValidation Study
In one paragraph
Observational study in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
11.8field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
125 citing papers in PubMed, 223 citations in OpenAlex.
- Micro/Nanostructured Materials and Microfluidic Diagnostic Platforms Enable Multimodal Detection of Circulating Tumor Cells.Exploration (Beijing, China) · 2026Review
- Reappraising the topology of cell-free fetal DNA in maternal blood toward improved prenatal genetic diagnostics.Science advances · 2026Review
- Non-Invasive Assessment of Microvascular Invasion Risk in Hepatocellular Carcinoma Using Liquid Biopsy: Translational Insights and Clinical Implications.Diagnostics (Basel, Switzerland) · 2026Review
- A Bioinspired Three-Dimensional High-Curvature Nano-Interface Integrated Microfluidic Chip for Small Extracellular Vesicles Enrichment and Machine Learning-Assisted Prostate Cancer Precision Diagnosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bioorthogonal Click Chemistry-Enabled Enrichment of Extracellular Vesicles for Integrated Molecular and Functional Liquid Biopsy§.Accounts of chemical research · 2026Article
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- Brain-Derived Extracellular Vesicle Subpopulations: from Bulk Measurements to Single-Entity Assays.JACS Au · 2026Review
- Plant-Derived Nanovesicles: A Comprehensive Review from Isolation to Clinical Translation-Unlocking Natural Nanocarriers for Biomedical Applications.Biomolecules · 2026Review
- Knowledge mapping of ⁹⁰Y transarterial radioembolization combined with immunotherapy in hepatocellular carcinoma: a bibliometric analysis.Discover oncology · 2026Article
- Advances in the mechanisms of extracellular vesicles and circulating tumor cells in hepatocellular carcinoma metastasis (Review).Molecular medicine reports · 2026Review
- Unlocking the Future of Hepatocellular Carcinoma Early Diagnosis: The Promise of Extracellular Vesicle Biomarkers.Journal of clinical and translational hepatology · 2026Review
- From cell lines to the clinic: identifying a urinary BlCa-EV signature through comparative proteomics of bladder cancer lysates and extracellular vesicles.Cell communication and signaling : CCS · 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
- 80 years of extracellular vesicles: from discovery to clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Lipid nanoparticles and extracellular vesicles: emerging cell free therapeutic platforms for hepatobiliary cancers.Frontiers in cell and developmental biology · 2026Review
- Deep Learning-Powered Nanoplasmonic Biosensing Approach Enables Ultrasensitive Extracellular Vesicles Profiling for Cancer Screening.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review: Detection of Cancer Biomarkers from a Clinical Perspective.International journal of molecular sciences · 2025Review
- Tumor Extracellular Vesicle Digital Scoring Assays for Cancer Detection and Monitoring.Precision chemistry · 2025Review
- A promising frontier of circulating messenger RNA in liquid biopsy: From mechanisms to clinical applications.International journal of cancer · 2025Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 5 institutions in 3 countries.
Na SunCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-3282-4405
Yi-Te LeeCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-8177-0407
Ryan Y ZhangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-3122-4053
Rueihung KaoCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Pai-Chi TengSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Yingying YangDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0001-6779-080X
Peng YangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-0861-9687
Jasmine J WangSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Matthew SmalleyCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-0509-6502
Pin-Jung ChenCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-5923-5299
Minhyung KimDivision of Cancer Biology and Therapeutics, Departments of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.ORCID http://orcid.org/0000-0002-5628-1062
Shih-Jie ChouCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Lirong BaoCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
Jing WangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-0515-9438
Xinyue ZhangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-2832-7895
Dongping QiCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0003-1624-8142
Juvelyn PalomiqueComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Nicolas NissenComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Steven-Huy B HanDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Saeed SadeghiDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Richard S FinnDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Sammy SaabDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Ronald W BusuttilDepartment of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Daniela MarkovicDepartment of Medicine, Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
David ElashoffDepartment of Medicine, Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Hsiao-Hua YuSmart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, 11529, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-3603-6932
Huiying LiCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0001-5633-5270
Anthony P HeaneyDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Edwin PosadasSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Sungyong YouSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.ORCID http://orcid.org/0000-0003-3513-1783
Ju Dong YangComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.ORCID http://orcid.org/0000-0001-7834-9825
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, 215123, Suzhou, P.R. China. rjpei2011@sinano.ac.cn.ORCID http://orcid.org/0000-0002-9353-3935
Vatche G AgopianDepartment of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. vagopian@mednet.ucla.edu.ORCID http://orcid.org/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, CA, 90095, USA. hrtseng@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-0942-5905
Yazhen ZhuCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA. yazhenzhu@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-2130-8085
California NanoSystems Institute · USUniversity of California, Los Angeles · USCedars-Sinai Medical Center · USInstitute of Chemistry, Academia Sinica · TWSuzhou Institute of Nano-tech and Nano-bionics · CN
Funding
Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5MThe 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
$9.5MThe 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 AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 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
$2.4MNovel Computation Methods for the Analysis of Cell-Free DNA Sequence DataR01CA246329 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M., LI, WENYUAN · 2019 to 2022
$2.2MClick 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 P30 CA016042NCI NIH HHS R01 CA218356NCI NIH HHS R01 CA246304NCI NIH HHS R01 CA246329NCI NIH HHS R01 CA253651NCI NIH HHS R01 CA255727NCI NIH HHS R21 CA216807NCI NIH HHS R21 CA235340NCI NIH HHS R21 CA240887NCI NIH HHS U01 CA198900NCI NIH HHS U01 CA230705NIBIB NIH HHS U01 EB026421
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%).
Indexed as
AgedBiomarkers, TumorCarcinoma, HepatocellularCase-Control StudiesClick ChemistryComputational ChemistryComputer SimulationDiagnosis, DifferentialDimethylpolysiloxanesDisease ProgressionEarly Detection of CancerExtracellular VesiclesFemaleHep G2 CellsHumansLab-On-A-Chip DevicesbaysilonBiomarkers, TumorDimethylpolysiloxanesRNA, Messenger
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