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Updated: Jun 28, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Monitoring Hepatocellular Carcinoma Using Tumor Content in Circulating Cell-Free DNA
Shifeng Lian1,2,3,4, Chenyu Lu5,6, Fugui Li3
1Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Sha Tin, Hong Kong SAR, People's Republic of China.
Purpose:
The objective of the study was to evaluate the use of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history.
Experimental Design:
We included 67 patients with hepatitis B virus-related HCC, of whom 17 had paired pre- and posttreatment samples, and 90 controls. Additionally, in a prospective cohort with hepatitis B virus 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 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), whereas it 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, the tumor content increased from 0.014 at 4 years before diagnosis to 0.026 at 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95% CI = 11.5%-37.8%) within 1 year before diagnosis to 30.4% (95% CI = 13.2%-52.9%) at the Barcelona Clinic Liver Cancer (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 1 yearearlier than clinical diagnosis and in predicting patient prognosis.
