The Urinary eccDNA Landscape in Prostate Cancer Reveals Associations with Genome Instability and Vital Roles in Cancer Progression

We pioneered the profiling of urinary cell-free eccDNAs landscape in PCa and uncovered a high association between eccDNA generation and active chromatin status as well as gene transcription. Double strand breaks and R-loops, which preferentially occur in active genomic sites and cause genome instability, can promote eccDNA generation. Genome instability frequently results in genomic mutations, and our study further established a link between eccDNA generation and oncogenic mutations. Additionally, genes specifically exhibiting high eccDNA generation frequency (HFGs) in PCa contributed to PCa progression and were associated with poorer survival outcomes in PCa patients. Finally, we demonstrated that eccDNAs derived from PCa-specific HFGs, in contrast to intergenic eccDNAs, could suppress PCa cell proliferation and migration, which was independent of their host gene expression.