Dataset Information

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

ABSTRACT:

Background

Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising.

Methods

A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort.

Findings

PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening.

Interpretation

Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care.

Funding

A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

SUBMITTER: Chen L

PROVIDER: S-EPMC10808903 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

Chen Lei L Wu Tong T Fan Rong R Qian Yun-Song YS Liu Jing-Feng JF Bai Jian J Zheng Bo B Liu Xiao-Long XL Zheng Dan D Du Lu-Tao LT Jiang Guo-Qing GQ Wang Ying-Chao YC Fan Xiao-Tang XT Deng Guo-Hong GH Wang Chun-Ying CY Shen Feng F Hu He-Ping HP Zhang Qing-Zheng QZ Ye Yi-Nong YN Zhang Jing J Gao Yan-Hang YH Xia Jie J Yan Hua-Dong HD Liang Min-Feng MF Yu Yan-Long YL Sun Fu-Ming FM Gao Yu-Jing YJ Sun Jian J Zhong Chun-Xiu CX Wang Yin Y Wang Hui H Kong Fei F Chen Jin-Ming JM Wen Hao H Wu Bo-Ming BM Wang Chuan-Xin CX Wu Lin L Hou Jin-Lin JL Wang Hong-Yang HY

EBioMedicine 20240106

<h4>Background</h4>Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising.<h4>Methods</h4>A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) ...[more]

PMID: 38184937

Similar Datasets

Project description:BackgroundAberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC).MethodsDifferentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples.ResultsBased on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969).ConclusionsWe have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort.Trial registrationThe study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

Dataset Information

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

Background

Methods

Findings

Interpretation

Funding

Publications

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

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