Circulating MicroRNAs in Serum of Human K-ras Oncogene Transgenic Rats With Pancreatic Ductal Adenocarcinomas

Objectives: Novel biomarkers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed because of its poor prognosis. We have previously established an animal model for human PDAC using transgenic rats in which expression of a human K-ras(G12V) oncogene is regulated by the Cre/lox system. Using this model, we searched for candidate circulating microRNAs (miRNAs) for use as novel clinical diagnostic biomarkers for PDAC. Methods: Rats bearing PDACs were generated using our model. MicroRNA expression in serum and pancreatic tissues of PDAC and control rats was compared by microarray analysis. Rat serum levels of 28 miRNAs identified by microarray analysis and 4 miRNAs previously reported to be high in plasma of PDAC patients were quantified by real-time quantitative reverse transcription polymerase chain reaction. Results: Quantification by real-time quantitative polymerase chain reaction revealed that miR-155, miR-21, and miR-210 were higher in serum of PDAC rats, similar to plasma of patients with PDAC. In addition, miR-18a, miR-203, miR-30b-5p, miR-31, miR-369-5p, miR-376a, and miR-541 were higher and miR-375 was lower in the serum of PDAC rats. Conclusion: We identified 4 previously unreported miRNAs (miRNA-203, miRNA-369-5p, miRNA-376a, and miRNA-375) whose expression is significantly different in PDAC rats compared to control rats. These miRNAs need to be quantitated in humans as potential novel clinical diagnostic biomarkers for PDAC.