Analysis of Methylation of Tumor-suppressive miRNAs and KRAS/TP53 Mutations in Pancreatic Juice

Abstract

Background/Aim: We previously reported the usefulness of detecting aberrant methylation in tumor suppressive microRNAs (miRNAs) in bile and plasma to discriminate pancreaticobiliary cancers from benign pancreaticobiliary diseases. This study analyzed the methylation of miRNAs in pancreatic juice to identify those specific to pancreatic cancer (PC). Patients and Methods: Pancreatic juice was collected from 20 patients with PC, including eight with intraductal papillary mucinous carcinoma (IPMC), two with low grade-pancreatic intraepithelial neoplasia (LG-PanIN), 32 with LG-intraductal papillary mucinous neoplasm (IPMN), and seven with benign pancreatic lesions. Polymerase chain reaction amplification and sequencing were performed for three tumor suppressive miRNAs (miR-200a, 200b, and 1247), and their methylation rates were determined. Additionally, KRAS and TP53 mutations were analyzed. Results: The methylation rate of miR-1247 was significantly higher in patients with PC than in those with LG-PanIN/IPMN. Furthermore, it was significantly higher in patients with IPMC than in those with LG-IPMN. KRAS and TP53 mutations were detected in seven (70%) and one (10%) of the patients with PC, respectively. Conclusion: Analyzing the methylation of miR-1247 in addition to KRAS and TP53 mutations in pancreatic juice may be useful to distinguish PC from PanIN/IPMN.