Inexpensive detecting of multiple cancers and other diseases from a single blood sample by analyzing circulating DNA fragments

Good news! Will we soon have much better and cheaper health checkups?

"UCLA scientists have developed a simple and cost-effective blood test that, in early studies, shows promise in detecting multiple cancers, various liver conditions and organ abnormalities simultaneously by analyzing DNA fragments circulating in the bloodstream. The test, described in the journal Proceedings of the National Academy of Sciences, could offer a powerful and more affordable approach to early disease detection and comprehensive health monitoring. ..."

"Key takeaways

• In early studies, the blood test, developed by UCLA scientists, shows promise in detecting multiple cancers.
• The new method, called MethylScan, works by analyzing cell-free DNA, tiny fragments of genetic material released into the blood when cells die.
• In tests, MethylScan detected about 63% of cancers across all stages and roughly 55% of early-stage cancers. 

..."

From the significance and abstract:

"Significance

Cell-free DNA (cfDNA) in blood carries molecular signals from multiple organs, offering a powerful, noninvasive way to detect disease and monitor health. Current cfDNA methylation tests are costly and usually focus on a single condition.

We developed MethylScan, a low-cost assay that sequences cfDNA methylome from blood. In over 1,000 individuals, MethylScan shows robust performance across a range of clinical applications, including multicancer detection in the general population, liver cancer surveillance in high-risk individuals, liver disease classification, organ injury detection, and ancestry prediction, all from one blood sample. This versatile approach enables affordable, wide-ranging cfDNA tests that can identify various health conditions simultaneously, with the potential to transform early disease detection and health monitoring across diverse clinical settings.

Abstract

Plasma cell-free DNA (cfDNA), originating from multiple organs, holds significant potential for noninvasive diagnostics and prognostics. Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci. In contrast, comprehensive profiling of cfDNA methylome can enable simultaneous detection of multiple diseases by capturing organ-specific methylation signatures, thereby offering a holistic view of health, when disease etiology is unclear or when conventional biochemical diagnostics are unavailable. However, deep sequencing required for sensitive detection of methylation abnormalities remains prohibitively expensive, limiting widespread clinical use. To overcome this barrier, we developed MethylScan, a highly cost-effective approach for cfDNA methylome sequencing. We demonstrated its broad clinical utility in a cohort of 1,061 individuals across diverse applications, including multicancer detection in general population, liver cancer surveillance in high-risk individuals, liver disease classification, identification of organ abnormalities, and race prediction from cfDNA.

In multicancer detection (liver, lung, ovarian, and stomach cancers), MethylScan achieved an area under the receiver operating characteristic curve (AUROC) of 0.938 (95% CI: 0.920 to 0.954), with a sensitivity of 63.3% (95% CI: 58.9 to 67.9%) at 98.0% specificity for all cancer stages.

For early-stage cancers, the AUROC was 0.916 (95% CI: 0.890 to 0.940), with 55.3% sensitivity (95% CI: 49.1 to 62.1%) at the same specificity.

In liver cancer surveillance, MethylScan achieved an AUROC of 0.927 (95% CI: 0.889 to 0.959), with 79.6% sensitivity (95% CI: 70.6 to 87.8%) at 90.4% specificity.

The assay also demonstrated strong performance in additional diagnostic tasks, supporting its potential as a versatile platform for comprehensive cfDNA-based health monitoring."

Detecting multiple cancers and other diseases from a single blood sample

UCLA researchers develop low-cost blood test to detect multiple cancers and other diseases from a single sample (original news release)

Toward the simultaneous detection of multiple diseases with a highly cost-effective cell-free DNA methylome test (open access)

Fig. 1 Illustration of the principle of the MethylScan assay and the criteria of choosing target regions of the MethylScan panel. Shown are four genomic regions, of which the middle two regions have consistent unmethylated MSRE cutting sites in the background cfDNA and are therefore included in the MethylScan panel.

In Step 1, upon MSRE digestion, the background cfDNA in the two panel regions are removed.

In Step 2, the target panel specifically captures cfDNA from the panel regions, thereby enriching tumor cfDNA in the final sequencing pool.

Fig. 4 Study design. (A) overview of plasma samples. (B–F) the usage of plasma samples in five studies. (G) the usage of tissue samples.