Abstract 4553: Evaluation of cfDNA release profiles in colorectal cancer patients during surgery

Abstract Surgical intervention is one of the most employed treatments for colorectal cancer, especially in patients with localized disease. However, the dynamics of circulating cell-free DNA (cfDNA) release during surgical procedures remain poorly understood. This lack of understanding underscores a significant gap regarding the biological processes underlying tumor response to surgery. Here we examined surgical cfDNA release from 30 colorectal cancer patients. cfDNA was extracted from plasma samples at three key points: preoperative (just before surgery), intraoperative (during surgery), and postoperative (at the end of surgery). Automated electrophoresis was used to analyze cfDNA concentrations and fragment sizes, which were then correlated with different clinical variables. Our findings show a significant increase in cfDNA release during and after surgery in comparison to preoperative time (2.8- and 2.2-fold higher, respectively). cfDNA fragments of <400 bp were predominant at all surgical stages, with no significant release of genomic DNA detected in any stage. We found that cfDNA concentrations increase on an average of 2 to 3-folds during and after surgery in patients over 60 years old, in patients with comorbidities and in patients with CEA levels > 5 ng/mL. Importantly, cfDNA release during surgery was significantly higher in patients with adverse clinical characteristics. Patients with locally advanced tumors or metastasis had a 3.1-fold increase in cfDNA release intraoperatively and a 2.4-fold increase postoperatively (p < 0.01). cfDNA concentrations also increase intraoperatively in patients with high tumor bud scores (2.6-fold higher, p < 0.02), perineural invasion (3.4-fold higher, p < 0.02), and lymphovascular invasion (3.1-fold higher, p < 0.05). Overall, our findings indicate that factors such as advanced physiological age, existing comorbidities, adverse clinical characteristics, and extensive surgical manipulation may contribute to increased tissue damage and enhanced cfDNA release. Citation Format: Mailson Alves Lopes, Maria Elvira Ribeiro Cordeiro, Flávio de Alencar Teles Barreto, Lara de Souza Moreno, André Araújo Silva, Mayra Veloso Soares, Mariana Braccialli de Loyola, Joao Batista de Sousa, Fabio Pittella-Silva. Evaluation of cfDNA release profiles in colorectal cancer patients during surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4553.