Cell-free DNA (cfDNA) fragmentome analysis can be used to detect hepatocellular carcinoma (HCC), according to research published in Cancer Discovery.

Researchers performed fragmentome analyses on 724 cfDNA samples from patients with HCC and patients who were at average or high risk of developing HCC. 

The researchers evaluated the fragmentation profiles of 473 nonoverlapping 5 MB regions consisting of roughly 80,000 fragments and spanning about 2.4 GB of the genome. 

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The results showed that patients with HCC had highly variable fragmentation profiles, whereas patients without cancer had consistent profiles. Patients with liver disease who did not have HCC, including patients with cirrhosis or viral hepatitis, had fragmentation profiles similar to those of other patients without cancer.

The researchers noted that cfDNA fragmentomes from HCC patients “represent a mixture of cfDNA profiles of chromatin compartments of cells from peripheral blood as well as those from liver cancer.” 

Patients with HCC had fragmentation profiles that demonstrated changes in transcription factors, chromatin, and chromosomal gains and losses. These changes were not present among patients without HCC, regardless of liver disease status.

The researchers used a machine learning model to determine if they could use changes in cfDNA fragmentomes to distinguish patients with HCC from those without HCC.

At a specificity of 98%, the model had a sensitivity of 88% for a population at average risk of HCC. At a specificity of 80%, the model had a sensitivity of 85% in a population at high risk of HCC.

“These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for non-invasive cancer detection,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Foda ZH, Annapragada AV, Boyapati K, et al. Detecting liver cancer using cell-free DNA fragmentomes. Cancer Discov. Published online November 18, 2022. doi:10.1158/2159-8290.CD-22-0659

This article originally appeared on Cancer Therapy Advisor