Evidence map›Paper›PMID 40500793›Full record

ArticleClinical epigenetics2025

A liquid biopsy approach detects HCC and identifies GJA4 as a potential biomarker for HBV-HCC via plasma cfDNA methylome profiling.

Jialing Sun, Xinfeng Sun, Weihuang He, Bingding Huang, Wenxing Feng, Zhiyi Han, Ruyun Ruan, Yuanke Pan, Jinxin Zhu, Jing Li and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

  1. Review
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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

20 authors.

Jialing Sun *Department of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Xinfeng Sun *Department of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Weihuang He *Shenzhen Rapha Biotechnology Incorporate, Shenzhen, 518118, China.
Bingding Huang *College of Big Data and Internet, Shenzhen Technology University, Shenzhen, 518118, China.
Wenxing Feng *Department of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Zhiyi HanDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Ruyun RuanCollege of Big Data and Internet, Shenzhen Technology University, Shenzhen, 518118, China.
Yuanke PanCollege of Big Data and Internet, Shenzhen Technology University, Shenzhen, 518118, China.
Jinxin ZhuCollege of Big Data and Internet, Shenzhen Technology University, Shenzhen, 518118, China.
Jing LiDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Xin ZhongDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Mengqing MaDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Rui HuDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Minling LvDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Qi HuangDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Wei ZhangDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Mingji FengShenzhen Rapha Biotechnology Incorporate, Shenzhen, 518118, China.
Jinyu YiDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
Pin CuiShenzhen Rapha Biotechnology Incorporate, Shenzhen, 518118, China. cuipin@rafabio.com.
Xiaozhou ZhouDepartment of Liver Disease, the Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China. zxz1006@gzucm.edu.cn.

Funding

the Natural Science Foundation of China 82374531the Project of Administration of Traditional Chinese Medicine of Guangdong Province of China 20231302the Shenzhen Science and Technology Project JCYJ20210324120405015the Shenzhen Science and Technology Project JCYJ20230807094802006
6 · The paper itself

Abstract

backgroundEarly detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. Plasma cfDNA methylation has been shown to have the potential to be a non-invasive method for diagnosing HCC. However, the identified HCC plasma cfDNA methylation sites were less sensitive to early HCC diagnosis. Therefore, we aimed to develop a highly sensitive marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC.

methodsThe study included 374 participants, including 102 healthy individuals, 51 HBV patients, 50 cirrhosis patients, and 171 HCC patients (56 at stage 0 or A according to BCLC staging). Two cfDNA methylation sequencing assays (whole genome bisulfite sequencing (WGBS) and targeted bisulfite sequencing (TBS)) were used along with machine learning modeling to detect HBV-related HCC based on differentially methylated regions (DMR) among the four participant groups.

resultsTBS analysis achieved an overall sensitivity of 96.67% at a specificity of 93.7% than alpha-fetoprotein (AFP) of 18%-60%, to discriminate all stages of HCC patients from healthy people, and sensitivity of 90.0% at a specificity of 93.75% to discriminate early-stage HCC patients from healthy people. A number of significant DMRs between HCC and non-cancer groups were identified, providing candidate biomarkers for HCC detection. Among these DMRs, one that locates in the promoter region of GJA4, was found to be consistently present in the whole process of HBV-related HCC carcinogenesis. Using data from TCGA, comparison of expression profile of GJA4 between 160 healthy people and 369 HCC patients further supported this scenario.

conclusionsThis study provides biomarkers for detecting, staging and early detection of HCC using plasma cfDNA methylome profiling. Additionally, the dynamic alteration of GJA4 promoter methylation may serve as a molecular clue for studying HBV-related HCC carcinogenesis and prognosis.

Indexed as

Carcinoma, HepatocellularCell-Free Nucleic AcidsLiver NeoplasmsAdultAgedBiomarkers, TumorCase-Control StudiesDNA MethylationEarly Detection of CancerFemaleHepatitis BHepatitis B virusHumansLiquid BiopsyMaleMiddle AgedBiomarkers, TumorCell-Free Nucleic AcidscfDNADMREarly detectionHBV-HCC carcinogenesisMethylation profile

Identifiers

PMID40500793
PMCPMC12160355

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