Evidence map›Paper›PMID 40307890›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Extracellular vesicle digital scoring assay for assessment of treatment responses in hepatocellular carcinoma patients.

Chen Zhao, Yi-Te Lee, Andrew Melehy, Minhyung Kim, Jacqueline Ziqian Yang, Ceng Zhang, Jina Kim, Ryan Y Zhang, Junseok Lee, Hyoyong Kim and 34 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

44 authors.

Chen ZhaoDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Yi-Te LeeKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Andrew MelehyDepartment of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Minhyung KimDepartment of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Jacqueline Ziqian YangDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Ceng ZhangDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Jina KimDepartment of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Ryan Y ZhangDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Junseok LeeDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Hyoyong KimDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Yong JuDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Yuan-Jen TsaiDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Xianghong Jasmine ZhouDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Steven-Huy B HanDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA.
Saeed SadeghiDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA.
Richard S FinnDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA.
Sammy SaabDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA.
David S LuDepartment of Interventional Radiology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Jason ChiangDepartment of Interventional Radiology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
Jae-Ho ParkKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Todd V BrennanDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Steven A WiselDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Manaf AlsudaneyComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Alexander KuoKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Walid S AyoubKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Hyunseok KimKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Hirsh D TrivediKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Yun WangKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Aarshi VipaniKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Irene K KimComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Tsuyoshi TodoComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Justin A SteggerdaComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Georgios VoidonikolasComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Kambiz KosariComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Nicholas N NissenComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Rola SaouafDepartment of Radiology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Amit G SingalDivision of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Myung Shin SimDepartment of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
David A ElashoffDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA.
Sungyong YouDepartment of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. sungyong.you@cshs.org.
Vatche G AgopianDepartment of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA. vagopian@mednet.ucla.edu.
Ju Dong YangKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. judong.yang@cshs.org.
Hsian-Rong TsengDepartment of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA. hrtseng@mednet.ucla.edu.
Yazhen ZhuDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA. yazhenzhu@mednet.ucla.edu.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
The UCLA Center in Early Detection of Liver CancerU01CA230705 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Vatche Agopian, Samuel Wheeler French · 2018 to 2026
$6.6M
Clinical Validation Center for Hepatocellular CarcinomaU01CA271887 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI FASIHA KANWAL, JORGE A MARRERO · 2022 to 2026
$4.7M
Non-Invasive Prenatal Diagnostics Based on Circulating TrophoblastsU01EB026421 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PISARSKA, MARGARETA, TSENG, HSIAN-RONG · 2019 to 2023
$4.0M
HCC 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
$3.3M
Extracellular Vesicle-Based Digital Scoring Assay for Detecting Early-stage Hepatocellular CarcinomaR01CA255727 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHU, YAZHEN · 2021 to 2025
$3.2M
Integrated analysis of HCC CTCs for Liver Transplant Candidate SelectionR01CA246304 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2020 to 2024
$2.8M
Click Chemistry-Mediated Surface Protein Assay for Quantifying Subpopulations of Hepatocellular Carcinoma-associated Extracellular VesiclesR01CA277530 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Vatche Agopian, HSIAN-RONG TSENG · 2023 to 2026
$2.6M
Developing and Automating an Extracellular Vesicle-Based Test for Early Detection of Hepatocellular CarcinomaR44CA288163 · NCI · EXIMIUS DIAGNOSTICS CORP · PI CHUANG, HAN-YU, LIU, SEAN XIAO · 2023 to 2025
$2.0M
Novel circulating biomarker digital scores for assessing treatment response in liver cancerK08CA259534 · NCI · CEDARS-SINAI MEDICAL CENTER · PI YANG, JU DONG · 2022 to 2024
$807k
Novel circulating biomarker digital scores for assessing treatment response in liver cancerR21CA280444 · NCI · CEDARS-SINAI MEDICAL CENTER · PI YANG, JU DONG, ZHU, YAZHEN · 2023 to 2023
$436k
Biomimetic NanoVilli Chips for Extracellular Vesicles in Hepatocellular CarcinomaR21CA240887 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2020 to 2021
$419k
NCI NIH HHS K08 CA259534NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA246304NCI NIH HHS R01 CA253651NCI NIH HHS R01 CA255727NCI NIH HHS R01 CA277530NCI NIH HHS R01CA277530, R01CA255727, R01CA253651, R01CA253651-04S1, R21CA280444, R01CA246304, U01EB026421, K08CA259534, R44CA288163, U01CA271887, and U01CA230705NCI NIH HHS R21 CA216807NCI NIH HHS R21 CA240887NCI NIH HHS R21 CA280444NCI NIH HHS R44 CA288163NCI NIH HHS U01 CA230705NCI NIH HHS U01 CA271887NIBIB NIH HHS U01 EB026421
6 · The paper itself

Abstract

backgroundThere are no validated biomarkers for assessing hepatocellular carcinoma (HCC) treatment response (TR). Extracellular vesicles (EVs) are promising circulating biomarkers that may detect minimal residual disease in patients with treated HCC.

methodsWe developed the HCC EV TR Score using HCC EV Digital Scoring Assay involving click chemistry-mediated enrichment of HCC EVs, followed by absolute quantification of HCC EV-specific genes by RT-digital PCR. Six HCC EV-specific genes were selected and validated through i) a comprehensive data analysis pipeline with an unprecedentedly large collection of liver transcriptome datasets (n = 9,160), ii) RNAscope validation on HCC tissues (n = 6), and iii) a pilot study on early- or intermediate-stage HCC and liver cirrhosis patients (n = 70). The performance of HCC EV TR Score was assessed in a phase-2 retrospective case-control study (n = 100).

resultsHCC EV TR Scores, calculated from pre- and post-treatment plasma samples in the phase-2 case-control study, accurately differentiated post-treatment viable from nonviable HCC in the training (area under the ROC curve [AUROC] of 0.90, n = 49) and validation set (AUROC of 0.88, n = 51). At an optimal cutoff of 0.76 identified in the training set, HCC EV TR Score had high accuracy in detecting viable tumors (sensitivity: 76.5%, specificity: 88.2%) and found residual disease not initially observed on MRI in six patients with a median lead time of 63 days.

conclusionsThis EV-based digital scoring approach shows great promise to augment cross-sectional imaging for the assessment of HCC treatment response.

Indexed as

Biomarkers, TumorCarcinoma, HepatocellularExtracellular VesiclesLiver NeoplasmsAdultAgedCase-Control StudiesFemaleHumansMaleMiddle AgedPilot ProjectsRetrospective StudiesTreatment OutcomeBiomarkers, TumorExtracellular VesicleHepatocellular CarcinomaLiquid BiopsyTreatment Responses

Identifiers

PMID40307890
PMCPMC12044846

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.