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Circulating cell-free DNA fragmentomics distinguishes pancreatic ductal adenocarcinoma from non-malignant conditions

Year: 2026

Type: article

Abstract: Purpose Pancreatic ductal adenocarcinoma (PDAC) has poor survival rates due to late diagnosis and limited early detection methods. Existing serum biomarkers have inadequate sensitivity and specificity. This study assessed whether circulating cell-free DNA (cfDNA) fragmentomic features could distinguish PDAC from chronic pancreatitis (CP) and healthy controls. Methods In this prospective single-center study, 83 participants were enrolled: 56 with histologically confirmed PDAC, 12 with CP, and 15 healthy controls. Plasma cfDNA was extracted from blood samples collected before intervention. cfDNA concentration, fragment length, total single nucleotide polymorphism (SNP) counts, and clinically relevant mutations were analyzed. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Results PDAC patients had significantly shorter cfDNA fragments (292.7 bp) than CP patients (313.9 bp; p = 0.047) and controls (315.7 bp; p = 0.003). cfDNA concentration was significantly higher in PDAC (45.6 ng/mL) than in CP (21.8 ng/mL; p = 0.026) and controls (20.2 ng/mL; p = 0.002). SNP counts and mutation numbers showed no significant differences. ROC analysis demonstrated moderate diagnostic accuracy for fragment length (AUC 0.770–0.820) and concentration (AUC 0.737–0.796). Conclusion Shorter cfDNA fragment length and higher concentration may help distinguish PDAC from CP and healthy individuals, supporting further investigation of cfDNA fragmentomics as a minimally invasive diagnostic tool.

Source: Langenbeck s Archives of Surgery

DOI: 10.1007/s00423-026-04267-0