Urine Cell-Free DNA in the Diagnosis of Intraductal Papillary Mucinous Neoplasms: A Prospective Observational Study

Intraductal papillary mucinous neoplasm (IPMN) is a typical precursor lesion of pancreatic cancer, but differential diagnosis and grading of IPMN is often difficult. Currently, grading of diagnosis is based mainly on imaging examinations, but these methods are invasive, and the accuracy is unsatisfactory. Therefore, the current study aimed to determine the usefulness of urine cell-free DNA (cfDNA) as a liquid biopsy, which the authors suggest has potential as a less invasive diagnostic tool for IPMN.

Preoperative plasma and urine samples were collected from 33 patients with a preoperative diagnosis of IPMN. From their plasma and urine, cfDNA was extracted. Analysis of GNAS and KRAS mutations in the cfDNA was performed using droplet digital polymerase chain reaction.

The final diagnosis was IPMN in 31 of the 33 cases according to the resected specimens. The positivity rate of GNAS mutations in these 31 patients was 10 % (3/31) in plasma cfDNA, and 32 % (10/31) in urine cfDNA. The positivity rate of KRAS mutations was 19 % (6/31) in plasma cfDNA and 58 % (18/31) in urine cfDNA. In the multivariate analysis of the malignancy diagnosis, the main pancreatic duct diameter was ≥10 mm, and the positivity of both GNAS and KRAS mutations in urine cfDNA were significantly associated with IPMN malignancy (odds ratio [OR], 12.70; P = 0.0200; OR, 8.10; P = 0.0269).

Urine cfDNA involves a less invasive liquid biopsy and seems to be useful in the diagnosis of IPMN.