Background: Precision medicine, allowing personalized immunosuppression optimization, may reduce organ rejection, especially in kidney transplant patients, where the rejection rate is ~10% in the first year post-transplant.1 Early detection of rejection and subsequent treatment in transplant patients may improve clinical outcomes.2 Donor-derived cell-free DNA (dd-cfDNA) in the plasma of transplant recipients has been used as a metric to determine graft injury due to immunologic rejection.2,3 Utilization of cfDNA as a biomarker is also clinical relevant in other disease conditions, such as cancers, stroke, autoimmune diseases and pregnancy related complications. Multiple clinical factors influence dd-cfDNA and background cfDNA levels. To better interpret the proportion of dd-cfDNA with respect to background cfDNA, we sought to understand the association of a number of factors, in over 1500 patient samples with early-stage cancer.
Methods: The impact of surgery/procedural trauma on the background cfDNA level was studied in early-stage cancer patients (n>1500) as well as healthy controls. cfDNA levels were quantified pre-surgery and post-surgery at various time points up to six weeks. For a subset of patients, regression analysis was performed to establish the relationship between total cfDNA levels with age and gender. Further subset analysis of the impact of concurrent medications, treatment-related adverse events, body mass index, and comorbidities on background cfDNA levels are currently underway.
Results and Discussion: Compared to the presurgical time point, plasma samples collected within the first four weeks post-surgery showed a significant increase in total cfDNA level (p<0.01). Background cfDNA level was found to be associated with increasing age but not gender.
Conclusion: cfDNA levels can be influenced by multiple factors including surgeries and patient age. Considering patient-related factors associated with background cfDNA may improve the clinician’s interpretation of dd-cfDNA results and patient outcomes.