Early-stage cancer results in a multiplicative increase in cell-free DNA originating from healthy tissue
Mamis, K.; Bozic, I.
Show abstract
Cell-free DNA (cfDNA) is a promising biomarker for cancer detection. However, cfDNA dynamics in the presence of cancer are still poorly understood. Leveraging a rich dataset of cfDNA in healthy individuals and early-stage cancer patients, we find a multiplicative increase in cfDNA concentration in the presence of cancer. This increase is cancer type-specific, ranging from a [~]1.3-fold increase in lung cancer, to a [~]12-fold increase in liver cancer, and does not originate from tumor, but from healthy tissue. Employing an additional dataset reporting the tissue of origin of cfDNA, we observe a significant increase in the correlation between cfDNA originating from leukocytes and from non-leukocyte sources in cancer patients. Introducing a mathematical model for cfDNA dynamics, we find that the observed correlation can be explained by a saturation mechanism in cfDNA clearance. Saturation in clearance implies that smaller increases in cfDNA shedding from healthy tissue due to cancer may lead to the larger observed multiplicative increases in cfDNA levels.
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