High Cell-Free DNA Integrity Is Associated with Poor Breast Cancer Survival

Cancers (Basel). 2021 Sep 18;13(18):4679. doi: 10.3390/cancers13184679.


Background: A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. Here, we provide further evidence to support the use of cfDI as a potential biomarker.

Methods: We selected 204 Eastern Finnish BC cases with non-metastatic disease and isolated cfDNA from the serum collected at the time of diagnosis before any treatment was given. The cfDConc and cfDI were measured with a fluorometer and electrophoresis and analyzed with 25 years of survival data.

Results: High cfDConc was not an independent prognostic factor in our analyses while high cfDI was found to be an independent prognostic factor for poor OS (p = 0.020, hazard ratio (HR) = 1.57, 95% confidence interval (CI) 1.07-2.29, Cox) and BCSS (p = 0.006, HR = 1.93, 95% CI 1.21-3.08)). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance.

Conclusions: Our results show high cfDI is an independent prognostic factor for poor OS and BCSS and improves the predictive performance of logistic regression models, thus supporting its prognostic potential.

Keywords: DNA fragmentation; biomarker; diagnostics; liquid biopsy.