AI-Powered DELFI Blood Test Validated for Liver Cancer Detection Across Diverse Populations
核心洞察
Researchers at Johns Hopkins Kimmel Cancer Center (搜索) validated the DELFI liquid biopsy platform for detecting liver cancer across geographically and biologically distinct populations from Guatemala and Romania.
The AI-powered test analyzes cell-free DNA fragmentation patterns and, when combined with AFP and clinical risk factors, identified early- and late-stage cancers with greater sensitivity than existing blood testing alone.
Using a new method called MethID, the team demonstrated that DELFI captures signals not only from tumor cells but also from liver cells, blood vessels, and immune cells responding to the cancer.
Researchers at the Johns Hopkins Kimmel Cancer Center (搜索) have validated an artificial intelligence-powered blood test that accurately detected liver cancer in individuals from two geographically and biologically distinct populations, while also uncovering the underlying biological signals that make the test effective. The findings, published July 31 in Cell Press Blue, build on the team's earlier development of the DELFI (DNA Evaluation of Fragments for Early Interception) liquid biopsy platform.
"Our earlier studies showed that fragmentome analyses could detect liver cancer and, more recently, chronic liver diseases that increase cancer risk," said Victor Velculescu, M.D., Ph.D., the Cancer Genetics and Epigenetics Professor, co-director of the cancer genetics and epigenetics program, and co-senior author of the study. "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."
The Unmet Need in Liver Cancer Screening
Liver cancer is one of the leading causes of cancer deaths worldwide, and its incidence continues to rise because of increasing rates of metabolic liver disease and other risk factors. Detecting liver cancer early dramatically improves treatment options, but current screening methods, which rely primarily on ultrasound imaging and the blood protein alpha-fetoprotein (搜索) (AFP), can miss many early cancers, the researchers explain.
Study Design and Cross-Population Validation
To determine whether the DELFI approach could reliably detect liver cancer regardless of its underlying cause, investigators analyzed blood samples from 377 people from Guatemala and Romania, with and without hepatocellular carcinoma (搜索), the most common form of liver cancer. The two populations represent markedly different causes of liver cancer. Most participants in Romania developed liver disease related to viral hepatitis or alcohol use, while participants in Guatemala primarily had metabolic liver disease, obesity and diabetes, with many also exposed to aflatoxin, a naturally occurring toxin linked to liver cancer.
Despite these differences, the blood test consistently detected liver cancer across both populations. When combined with AFP and simple clinical risk factors, such as age and sex, the approach identified early- and late-stage cancers with greater sensitivity than existing blood testing alone.
Uncovering Biological Signals with MethID
Using a newly developed method for tracing where DNA fragments originate, called MethID, the team showed that the DELFI test works because it captures more than signals from tumor cells. It also captures signals from liver cells, blood vessels and immune cells responding to the cancer.
"As a result, these DNA fragments contain much more information than whether cancer is present," said Zachariah Foda, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and co-senior author of the study. "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."
Population-Specific Molecular Signatures
The researchers also identified molecular signatures that differed between populations. For example, they detected a distinctive mutation pattern across the genome associated with aflatoxin exposure in participants from Guatemala, but they also showed that the overall fragmentome classifier remained effective regardless of the underlying cause of the liver cancer.
The study suggests that genome-wide fragmentome analysis captures both universal biological features of liver cancer and region-specific molecular changes, making it adaptable to diverse patient populations around the world.
Broader Implications for Liquid Biopsy Technology
The findings extend the researchers' broader vision for fragmentome technology, suggesting that genome-wide analysis of cell-free DNA could ultimately provide a foundation for noninvasive blood tests capable of detecting multiple diseases using a common technology platform. Velculescu and colleagues working with DELFI Diagnostics (搜索) recently reported the clinical validation of a blood test for lung cancer screening, called FirstLook Lung (搜索), which is already available in certain health systems nationwide.
The investigators 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.
This research was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Commonwealth Foundation, the Cole Foundation, a research grant from Delfi Diagnostics (搜索), National Institutes of Health grants CA121113, CA006973, CA233259, CA062924, CA271896, T32GM136577, and T32GM007814-40, and Department of Defense grant HT94252510480.