A novel artificial intelligence blood test technology developed and used by researchers at the Johns Hopkins Kimmel Cancer Center to successfully detect lung cancer in a 2021 study has now detected more than 80% of liver cancers in a new study of 724 people .
The blood test called DELFI (DNA Evaluation of Fragments for Early Interception) detects fragmentation changes in the DNA of cancer cells released into the bloodstream, known as cell-free DNA (cfDNA). In the most recent study, researchers used DELFI technology on blood plasma samples from 724 people in the United States, the European Union (EU) and Hong Kong to detect hepatocellular cancer (HCC), a type of liver cancer.
The researchers believe this is the first genome-wide fragmentation analysis to be independently validated in two high-risk populations and across different racial and ethnic groups with different causes associated with liver cancer.
Their findings were reported on November 18 cancer discovery and at the American Association for Cancer Research Special Conference: Precision Prevention, Early Detection, and Interception of Cancer.
According to a global analysis of the burden of liver disease (J. Hepatology2019).
“Increased early detection of liver cancer could save lives, but currently available screening tests are underused and miss many types of cancer,” said Victor Velculescu, MD, Ph.D., professor of oncology and co-director of the Cancer Genetics and Epigenetics program at the Johns Hopkins Kimmel Cancer Center, who co-authored the study with Zachariah Foda, MD, Ph.D., gastroenterologist, Akshaya Annapragada, MD/Ph.D. directed. student, and Amy Kim, MD, assistant professor of medicine at Johns Hopkins University School of Medicine.
Of the 724 plasma samples examined, 501 were collected in the US and EU and included samples from 75 people with HCC to train and validate the machine learning model, a type of artificial intelligence that uses data and algorithms to improve accuracy, explains Foda . An additional 223 plasma samples from individuals in Hong Kong were analyzed for validation, including samples from 90 individuals with HCC, 66 with hepatitis B virus (HBV), 35 with HBV-related liver cirrhosis, and 32 individuals with no underlying risk factors.
DELFI technology uses a blood test to measure how DNA is packaged in the nucleus by examining the size and amount of cell-free DNA present in the circulation from different regions of the genome. Healthy cells pack the DNA like a well-stocked suitcase in which different regions of the genome are carefully placed in different compartments. In contrast, the nuclei of cancer cells are rather disorganized suitcases into which items from across the genome are thrown at random. When cancer cells die, they chaotically release fragments of DNA into the bloodstream.
DELFI identifies the presence of cancer by examining millions of cfDNA fragments for abnormal patterns, including the size and amount of DNA in different regions of the genome. The DELFI approach requires only low-coverage sequencing, making this technology cost-effective in a screening setting, the researchers say.
In the latest study, the researchers performed the test – previously shown to accurately classify lung cancer – on cfDNA fragments isolated from the plasma samples. They analyzed the fragmentation patterns in each sample to develop a DELFI score.
Scores were low for cancer-free individuals with viral hepatitis or cirrhosis (mean DELFI score was 0.078 and 0.080, respectively), but averaged 5-10 times higher for the 75 HCC patients in the US/EU high-risk samples Scores observed at all cancer stages, including early disease (DELFI scores for Stage 0 = 0.46, Stage A = 0.61, Stage B = 0.83, and Stage C = 0.92). In addition, the test detected fragmentation changes in the content and packaging of liver cancer genomes, including genomic regions associated with liver-specific activity.
The DELFI technology detected liver cancer in its earliest stages with an overall sensitivity – or ability to accurately detect a cancer – of 88% and a specificity of 98%, meaning it almost never gave a false positive result in people at intermediate Risk. In samples collected from individuals at high risk of HCC, the test had a sensitivity of 85% and a specificity of 80%.
“Currently, less than 20% of the high-risk population is screened for liver cancer due to accessibility and suboptimal test performance. This new blood test can double the number of liver cancer cases detected compared to the available standard blood test and increase cancer screening,” says Kim, co-senior author of the study.
The researchers say next steps include validating this approach in larger studies for clinical use.
Liver cancer is diagnosed in more than 800,000 people worldwide each year, according to the American Cancer Society, and is a leading cause of cancer-related deaths worldwide.
Besides Velculescu, Foda, Annapragada and Kim, other researchers were Kavya Boyapati, Daniel Brahm, Nicholas Vulpescu, Jamie Medina, Dimitrios Mathios, Stephen Cristiano, Noushin Niknafs, Harry Luu, Michael Goggins, Robert Anders, Jing Sun, Shruti Meta, David Thomas, Gregory Kirk, Vilmos Adleff, Jillian Phallen and Robert Scharpf.
The research was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Stand Up to Cancer-Dutch Cancer Society International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1415), The Gray Foundation, The Commonwealth Foundation, SU2C INTIME Lung Cancer Interception Dream Team Grant, the Mark Foundation for Cancer Research, a research grant from Delfi Diagnostics, the National Institutes of Health grants CA121113, CA006973, CA233259, GM136577, CA237624, and CA062924, and the Department of Defense CDMRP Award W81XWH-20-1-0605. Stand Up to Cancer is an Entertainment Industry Foundation program administered by the American Association for Cancer Research.
The researchers disclose the following competing interests: Velculescu is a founder of Delfi Diagnostics, serves on the board of directors and as an advisor to that organization, and owns shares in Delfi Diagnostics, which are subject to certain restrictions under Johns Hopkins University policies. In addition, Johns Hopkins University owns shares in Delfi Diagnostics. Velculescu sold its stake in Personal Genome Diagnostics (PGDx) to LabCorp in February 2022. He is the inventor of patent applications filed by Johns Hopkins University related to cancer genomic analysis and cell-free DNA for cancer detection and licensed to one or more companies including Delfi Diagnostics, LabCorp, Qiagen, Sysmex, Agios, Genzyme, Esoterix, Ventana and ManaT Bio. Under these license agreements, the university and the inventors are entitled to fees and royalties. Velculescu is a consultant to Danaher, Takeda Pharmaceuticals and Viron Therapeutics. Scharpf is the founder and advisor of Delfi Diagnostics and owns stock of Delfi Diagnostics, subject to certain university policy restrictions. These agreements have been reviewed and approved by Johns Hopkins University in accordance with its Conflicts of Interest Policy.