The fragmentome technology identifies hepatocellular carcinoma in populations with different underlying risk factors and causes of liver disease.
Researchers at the Johns Hopkins Kimmel Cancer Center validated an artificial intelligence-powered blood test that accurately detected liver cancer in two geographically and biologically distinct populations while identifying the biological signals that drive the test’s effectiveness.
The study, published in Cell Press Blue, utilized the DNA Evaluation of Fragments for Early Interception (DELFI) liquid biopsy platform to analyze millions of fragments of cell-free DNA circulating in the bloodstream. This validation follows research from March 2026 showing that genome-wide fragmentome technology could detect liver fibrosis and cirrhosis, conditions that often precede liver cancer.
“Our earlier studies showed that fragmentome analyses could detect liver cancer and, more recently, chronic liver diseases that increase cancer risk,” says Victor Velculescu, MD, PhD, the cancer genetics and epigenetics professor, co-director of the cancer genetics and epigenetics program, and co-senior author of the study, in a release. “This study demonstrates that the approach works with high performance across different patient populations while revealing the biological signals in the bloodstream that make this type of detection possible.”
Validation Across Diverse Risk Factors
To determine if the DELFI approach could reliably detect liver cancer regardless of the underlying cause, investigators analyzed blood samples from 377 individuals from Guatemala and Romania. The study included participants with and without hepatocellular carcinoma, the most common form of liver cancer.
The two populations represented different primary causes of liver disease. Participants in Romania largely developed disease related to viral hepatitis or alcohol use, while those in Guatemala primarily had metabolic liver disease, obesity, and diabetes, with some exposed to aflatoxin, a naturally occurring toxin linked to cancer.
Despite these differences, the blood test consistently detected liver cancer across both groups. When combined with the blood protein alpha-fetoprotein and clinical risk factors such as age and sex, the approach identified early- and late-stage cancers with greater sensitivity than existing blood testing alone.
Tracing DNA Origins
Using a newly developed method for tracing the origin of DNA fragments called MethID, the research team found that the DELFI test captures signals from tumor cells as well as liver cells, blood vessels, and immune cells responding to the malignancy.
“As a result, these DNA fragments contain much more information than whether cancer is present,” says Zachariah Foda, MD, PhD, assistant professor of medicine at the Johns Hopkins University School of Medicine and co-senior author of the study, in a release. “It tells us where these fragments originate and how they change during cancer development, allowing us to better understand the biology of the disease and improve our ability to detect it.”
The study also identified molecular signatures that differed between populations, such as a distinctive mutation pattern associated with aflatoxin exposure in participants from Guatemala. However, the overall fragmentome classifier remained effective regardless of the underlying cause of the liver cancer.
Researchers say future studies will focus on prospective clinical validation and further refining multimodal liquid biopsy approaches that combine fragmentome analysis with protein biomarkers and clinical risk factors to improve early detection of liver cancer.
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