New method analyzes DNA methylation in cell-free DNA to identify organ damage and disease signals with reduced sequencing requirements.
Researchers have developed a simple blood test that shows promise in detecting multiple cancers, various liver conditions, and organ abnormalities simultaneously by analyzing DNA fragments in the bloodstream.
The study, published in the Proceedings of the National Academy of Sciences, describes a method called MethylScan. This approach analyzes cell-free DNA (cfDNA), which are small fragments of genetic material released into the blood when cells die. Because cells from every organ shed DNA into the bloodstream, cfDNA carries molecular signals that reflect health status throughout the body.
“Early detection is crucial,” says Jasmine Zhou, PhD, the study’s senior author, a professor of pathology and laboratory medicine and investigator at the UCLA Health Jonsson Comprehensive Cancer Center, in a release. “Survival rates are far higher when cancers are caught before they spread. If you detect cancer at stage one, outcomes are dramatically better than at stage four.”
While existing liquid biopsy tests often look for mutations in tumor DNA, they can be expensive and require deep sequencing. Instead of searching for mutations, the research team examined DNA methylation, which are chemical tags attached to DNA that help regulate gene activity. Methylation patterns differ by tissue type and change when cells become diseased.
“DNA methylation reflects the health status of a tissue,” says Dr Wenyuan Li, a professor of pathology and laboratory medicine at UCLA and co-corresponding author of the study, in a release. “It’s a very informative signal.”
Reducing Background Noise in Sequencing
A challenge in cfDNA testing is that 80% to 90% of the fragments originate from normal blood cells, creating background noise that makes it difficult to detect rare fragments from early-stage tumors. To address this, the researchers used specialized enzymes to selectively cut away unmethylated DNA fragments.
This process enriches the sample for methylated DNA from solid organs, reducing the amount of sequencing data required. The researchers say this technique could lower sequencing costs to less than $20 per sample if the price per gigabase is under $4.
Study Results and Tissue of Origin
In a study of blood samples from 1,061 people, the test achieved 98% specificity for multi-cancer detection. It detected approximately 63% of cancers across all stages and roughly 55% of early-stage cancers. Beyond detection, the methylation patterns helped identify the tissue of origin, which is necessary for directing follow-up diagnostic procedures to the correct organ.
The test also showed efficacy in liver cancer surveillance for high-risk individuals, including those with liver cirrhosis or hepatitis B virus (HBV). It detected nearly 80% of cases at a specificity of just over 90%. Additionally, the blood test distinguished between different types of liver disease, such as viral hepatitis and metabolic-associated liver disease, correctly classifying about 85% of patients. This capability suggests that blood-based DNA testing could eventually reduce the need for invasive liver biopsies.
“This study demonstrates that blood-based methylation profiling can deliver clinically meaningful information across multiple diseases,” says Zhou in a release.
The researchers note that larger prospective trials are needed to confirm the test’s performance in real-world screening environments. The work was supported in part by grants from the National Cancer Institute.
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