Pancreatic ductal
adenocarcinoma (PDAC) is one of the most fatal
cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary
mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of
miRNAs in the progression of IPMNs to
malignancy, and we hypothesized that
miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of
miRNAs in archived preoperative plasma from individuals with pathologically confirmed IPMNs and healthy controls and discover plasma
miRNAs that distinguish between IPMN patients and controls and between "malignant" and "benign" IPMNs. Using novel nCounter technology to evaluate 800
miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P = 0.002]. The signature contained novel
miRNAs and
miRNAs previously implicated in pancreatic
carcinogenesis that had 2- to 4-fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive
carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6-73.2, P = 0.005), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct
miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a
miRNA-based blood test to aid in the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment.