Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options, and early detection remains challenging due to the lack of reliable non-invasive biomarkers. This study investigated plasma and urine circulating tumor deoxyribonucleic acid (ctDNA) methylation profiles as potential biomarkers for PDAC detection. A total of 35 patients with PDAC and 10 non-cancerous controls were enrolled, and whole-genome bisulfite sequencing was performed on ctDNA extracted from both plasma and urine samples. Plasma ctDNA methylation profiles effectively distinguished cancerous from non-cancerous samples, particularly through differential methylation in intergenic regions. Hierarchical clustering further enabled the accurate grouping of patients with PDAC. However, urine ctDNA did not show significant methylation differences. These findings suggest that plasma ctDNA methylation holds promise as a non-invasive biomarker for PDAC detection, whereas urine ctDNA appears less informative. Future research should validate these findings in larger cohorts and investigate machine learning approaches to improve diagnostic performance, ultimately facilitating earlier detection and improved patient outcomes.