Evidence map›Paper›PMID 38741204›Full record

ArticleClinical and translational medicine2024

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

De-Zhen Guo, Ao Huang, Ying-Chao Wang, Shuang Zhou, Hui Wang, Xiang-Lei Xing, Shi-Yu Zhang, Jian-Wen Cheng, Ke-Hui Xie, Qi-Chang Yang and 9 more

Registry-linked trialAbstract readMulticenter Study
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07489768 (A Prospective, Multicenter Observational Clinical Study of the GNB4 and Riplet Gene Methylation Combined Detection Kit), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
–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.

NCT07489768 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Prospective, Multicenter Observational Clinical Study of the GNB4 and Riplet Gene Methylation Combined Detection Kit (Real-time PCR) for Post-treatment Recurrence Monitoring in Hepatocellular Carcinoma

TypeobservationalSponsorTongji HospitalRan2026 to 2029Enrolled162ConditionsHepatocellular Carcinoma (HCC), Hepatocellular Carcinoma RecurrentArmsGNB4 and Riplet Gene Methylation Combined Detection Kit (Real-time PCR)
3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  11. [Expert consensus on the diagnosis, treatment, and management of liver nodules (version 2026)].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
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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

19 authors.

De-Zhen GuoDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.ORCID 0000-0002-6132-5269
Ao HuangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
Ying-Chao WangThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China.
Shuang ZhouSinglera Genomics Ltd., Shanghai, China.
Hui WangSinglera Genomics Ltd., Shanghai, China.
Xiang-Lei XingBiliary Tract Surgery Department IV, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Shi-Yu ZhangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
Jian-Wen ChengDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
Ke-Hui XieSinglera Genomics Ltd., Shanghai, China.
Qi-Chang YangSinglera Genomics Ltd., Shanghai, China.
Cheng-Cheng MaSinglera Genomics Ltd., Shanghai, China.
Qing LiDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yan ChenXiangYa Medical Laboratory, Central South University, Changsha, Hunan, China.
Zhi-Xi SuSinglera Genomics Ltd., Shanghai, China.
Jia FanDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
Rui LiuSinglera Genomics Ltd., Shanghai, China.
Xiao-Long LiuThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, P. R. China.ORCID 0000-0002-3096-4981
Jian ZhouDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
Xin-Rong YangDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.ORCID 0000-0002-2716-9338

Funding

Eastern Talent ProgramNational Key Research and Development Program of China 2019YFC1315800National Key Research and Development Program of China 2019YFC1315802National Key Research and Development Program of China 2021YFC2501900National Natural Science Foundation of China 82072715National Natural Science Foundation of China 82341027Original Discovery Program of National Natural Science of China 82150004Science Foundation of Zhongshan Hospital, Fudan University 2020ZSLC31Science Foundation of Zhongshan Hospital, Fudan University 2021ZSCX28Shanghai Hospital Development Center SHDC2023CRD025Shanghai Municipal Health Commission 201940075Shanghai Municipal Health Commission 2022LJ005Shanghai Municipal Health Commission Collaborative Innovation Cluster Project 2019CXJQ02Shanghai Science and Technology Commission 21140900300Shanghai Science and Technology Commission 22S31901800State Key Program of National Natural Science of China 81830102
6 · The paper itself

Abstract

backgroundEarly diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC.

methodsA three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP).

resultsGenome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001).

conclusionsHepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Indexed as

Carcinoma, HepatocellularDNA MethylationEarly Detection of CancerLiver NeoplasmsAdultAgedBiomarkers, TumorCirculating Tumor DNACohort StudiesFemaleHumansMaleMiddle AgedPrognosisBiomarkers, TumorCirculating Tumor DNAcirculating tumour DNA methylationdiagnosishepatocellular carcinomaliquid biopsyprognosis

Identifiers

PMID38741204
PMCPMC11091019

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Registered trials

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.