Circulating extracellular vesicle-encapsulated microRNA as screening biomarkers for intraductal papillary mucinous neoplasm.

Abstract

Since intraductal papillary mucinous neoplasms (IPMNs) occasionally contain pancreatic malignancies, it is vital to develop a screening program that can detect IPMNs in the general population and that can identify IPMNs with high malignant potential. The present study investigated whether microRNAs (miRNAs/miRs) in the blood may be diagnostic markers for IPMN screening. Initially, extracellular vesicle-encapsulated miRNAs (EV-miRNAs) in the serum with altered expression between IPMN, IPMN-derived carcinoma (IPMC) and control samples, were identified using microarray analysis. To validate the microarray results, the expression levels of selected EV-miRNAs were detected. Briefly, serum EV-miRNAs were extracted from 38 patients with IPMN (11 patients with IPMC and 27 patients with benign IPMN) and 21 non-tumor controls. The results of the microarray analysis revealed that the expression levels of EV-miR-22-3p, EV-miR-4539 and EV-miR-6132 were higher in the IPMN and IPMC serum samples compared with those in the control samples. With regards to discriminating IPMNs from controls, only miR-4539 exhibited a significant difference (P=0.004). In the comparison between IPMN and IPMC, carcinogenic antigen 19-9 (CA19-9) and EV-miR-6132 exhibited significant differences (P=0.01 and P=0.007, respectively). Receiver operating characteristic (ROC) curve analysis demonstrated that EV-miR-4539 could discriminate patients with IPMNs from control patients, with an area under the curve (AUC) of 0.72. Additionally, ROC analysis indicated that the markers could discriminate patients with IPMC from benign IPMN, with AUC values of 0.77 for EV-miR-6132 and 0.74 for CA19-9. In conclusion, the present study suggested that EV-miRNAs may be used as diagnostic markers for the detection of IPMNs in the general population as well as for identifying IPMNs with high malignant potential.