Impact of WWP1-Encoded Extrachromosomal DNA on Chemoresistance in Ovarian Cancer

Background Ovarian cancer is one of the most lethal gynecological malignancies, primarily due to chemoresistance, which complicates effective treatment. Extrachromosomal circular DNA (eccDNA) has recently been implicated in cancer progression and drug resistance, yet its specific contributions remain underexplored. This study investigates the role of WWP1-encoded eccDNA (WWP1-eccDNA) in fostering drug resistance in ovarian cancer cells. Objective To elucidate the impact of WWP1-eccDNA on the chemoresistance of ovarian cancer cells and assess the efficacy of digital PCR (ddPCR) compared to quantitative PCR (qPCR) in detecting this eccDNA under various treatment conditions. Methods We utilized human ovarian cancer SKOV3 cells and their cisplatin-resistant variant, SKOV3/DDP. Following eccDNA extraction, BALB/cA-nu female mice were treated with saline, cisplatin, or hydroxyurea. The expression levels of WWP1-eccDNA were quantitatively analyzed using ddPCR and qPCR to compare the methodologies' sensitivity and accuracy. Results ddPCR demonstrated superior sensitivity and accuracy in detecting WWP1-eccDNA compared to qPCR. Treatment with cisplatin significantly increased the levels of WWP1-eccDNA in SKOV3 cells, whereas hydroxyurea treatment reduced these levels in SKOV3/DDP cells, highlighting the potential modulatory effects of these treatments on eccDNA abundance. Conclusion WWP1-eccDNA contributes to the chemoresistance observed in ovarian cancer cells. The enhanced sensitivity of ddPCR suggests its utility in eccDNA research and potential for clinical applications in diagnosing and monitoring resistance patterns. These insights are foundational to developing targeted therapies that could disrupt eccDNA-mediated resistance mechanisms.