Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA

Shifeng Lian; Chenyu Lu; Fugui Li; Xia Yu; Limei Ai; Biaohua Wu; Xueyi Gong; Wenjing Zhou; Xuejun Liang; Jiyun Zhan; Yong Yuan; Fang Fang; Zhiwei Liu; Mingfang Ji; Zongli Zheng

doi:10.1158/1078-0432.CCR-23-3449

Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA

Shifeng Lian, Chenyu Lu, Fugui Li, Xia Yu, Limei Ai, Biaohua Wu, Xueyi Gong, Wenjing Zhou, Xuejun Liang, Jiyun Zhan, Yong Yuan, Fang Fang, Zhiwei Liu^*, Mingfang Ji^*, Zongli Zheng^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

5 Citations (Scopus)

Abstract

Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history.

Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA.

Results: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C.

Conclusions: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

Original language	English
Pages (from-to)	2772–2779
Number of pages	8
Journal	Clinical Cancer Research
Volume	30
Issue number	13
Online published	1 Jul 2024
DOIs	https://doi.org/10.1158/1078-0432.CCR-23-3449
Publication status	Published - 1 Jul 2024

Funding

We thank all the participants in this study for their contribution to the research. This study was supported by the Lau Grant (LC230003), the Swedish Research Council (202001418) and the Research Grants Council of the Hong Kong Special Administrative Region (11103024 and T12-101/23-N) to Z. Zheng, and the China Scholarship Council (201808440263) to S. Lian.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

circulating cell-free DNA
copy number
tumor fraction
hepatocellular carcinoma
early detection
population-based cancer screening

RGC Funding Information

RGC-funded

Access Output

10.1158/1078-0432.CCR-23-3449

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

TBRS: Single-Cell Multi-Omics Study of Atherosclerotic Vascular Disease: Narrowing the Gap Between Bench and Bedside
HUANG, Y. (Principal Investigator / Project Coordinator), CAI, Z. (Co-Principal Investigator), LUI, K.O.-L. (Co-Principal Investigator), MA, R. C. W. (Co-Principal Investigator), WANG, L. (Co-Principal Investigator), Xu, A. (Co-Principal Investigator), YU, W. (Co-Principal Investigator), Chan, T. F. (Co-Investigator), TIAN, X. (Co-Investigator), XIA, Y. (Co-Investigator), YIN, H. (Co-Investigator), YIU, K. H. (Co-Investigator), ZHANG, L. (Co-Investigator), ZHENG, Z. (Co-Investigator), ZHOU, B. (Co-Investigator) & HAN, Q. (Collaborator)
1/01/24 → …
Project: Research

Cite this

@article{d51ceeb367bc4838a80e6723492f91cf,

title = "Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA",

abstract = "Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history.Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA.Results: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C.Conclusions: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.",

keywords = "circulating cell-free DNA, copy number, tumor fraction, hepatocellular carcinoma, early detection, population-based cancer screening",

author = "Shifeng Lian and Chenyu Lu and Fugui Li and Xia Yu and Limei Ai and Biaohua Wu and Xueyi Gong and Wenjing Zhou and Xuejun Liang and Jiyun Zhan and Yong Yuan and Fang Fang and Zhiwei Liu and Mingfang Ji and Zongli Zheng",

year = "2024",

month = jul,

day = "1",

doi = "10.1158/1078-0432.CCR-23-3449",

language = "English",

volume = "30",

pages = "2772–2779",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research",

number = "13",

}

TY - JOUR

T1 - Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA

AU - Lian, Shifeng

AU - Lu, Chenyu

AU - Li, Fugui

AU - Yu, Xia

AU - Ai, Limei

AU - Wu, Biaohua

AU - Gong, Xueyi

AU - Zhou, Wenjing

AU - Liang, Xuejun

AU - Zhan, Jiyun

AU - Yuan, Yong

AU - Fang, Fang

AU - Liu, Zhiwei

AU - Ji, Mingfang

AU - Zheng, Zongli

PY - 2024/7/1

Y1 - 2024/7/1

N2 - Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history.Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA.Results: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C.Conclusions: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

AB - Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history.Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA.Results: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C.Conclusions: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

KW - circulating cell-free DNA

KW - copy number

KW - tumor fraction

KW - hepatocellular carcinoma

KW - early detection

KW - population-based cancer screening

U2 - 10.1158/1078-0432.CCR-23-3449

DO - 10.1158/1078-0432.CCR-23-3449

M3 - RGC 21 - Publication in refereed journal

C2 - 38630548

SN - 1078-0432

VL - 30

SP - 2772

EP - 2779

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 13

ER -

Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA

Abstract

Funding

UN SDGs

Research Keywords

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Fingerprint

Projects

TBRS: Single-Cell Multi-Omics Study of Atherosclerotic Vascular Disease: Narrowing the Gap Between Bench and Bedside

Cite this