Circulating extrachromosomal circular DNA in epithelial ovarian cancer reflects chemotherapeutic response and recurrence
Cell-free extrachromosomal circular DNA (eccDNA) in the plasma provides an advantage for monitoring epithelial ovarian cancer (EOC) progression. We isolated eccDNA from plasma samples of 30 EOC patients before treatment (T0 time point) and 4 healthy individuals. We followed 16 EOC patients, collecting paired eccDNA samples between the 3rd and 4th course of chemotherapy (T1) and 6 months after the last course of chemotherapy (F). The patients were divided into three groups, including complete remission (CR) group, partial remission group (PR), and relapse group (RC). We compared the normalized eccDNA count per million mapped reads (EPM) among all the groups and assessed the distribution of eccDNA on each chromosome. Then, the eccDNA within the top 5 % coverage regions of each chromosome were annotated, and the top genes were analyzed for prognosis. We found that EOC patients exhibited significantly higher levels of eccDNA, with higher coverage in coding exon regions. Notably, circulating eccDNA was generally increased in the CR group, while decreased in the PR and RC group during treatment. Our results showed that the fold change of EPMs between the T1 and T0 distinguished PR and RC patients from CR patients, with area under the curve (AUC) of 0.71. Additionally, we identified two genes, SCARB1 and PDE10A, whose EPMs were able to predict prognosis in EOC patients, with AUCs of 0.86 and 0.83, respectively. Thus, our study offers valuable preliminary insights into a novel approach for predicting chemotherapy sensitivity in EOC patients, based on the trends of circulating eccDNA.
