Extracellular vesicle-derived microRNAs in pancreatic juice as biomarkers for detection of pancreatic ductal adenocarcinoma

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in an advanced stage, with minimal likelihood of long-term survival. Only a small subset of patients are diagnosed with early (T1) disease. Early detection is challenging due to the late onset of symptoms and limited visibility of sub-centimeter cancers on imaging. A novel approach is to support the clinical diagnosis with molecular markers. MicroRNA derived from extracellular vehicles (EVs) in blood has shown promise as a potential biomarker for pancreatic neoplasia, but microRNA derived from pancreatic juice (PJ) may be a more sensitive biomarker, given that is in close contact with ductal cells from which PDAC arises. This study aims to evaluate and compare the performance of PJ- and serum-derived EV-miRNA for the detection of PDAC.

Methods: PJ was collected from the duodenum during EUS after secretin stimulation from 54 patients with PDAC and 118 non-malignant controls. Serum was available for a subset of these individuals. MiR-16, miR-21, miR-25, miR-155 and miR-210 derived from EVs isolated from PJ and serum were analyzed by qPCR, and serum CA19-9 levels were determined by electrochemiluminescence immunoassay. For statistical analysis, either a Mann-Whitney U test or a Wilcoxon Signed Rank test was performed. ROC curves and AUC were used to assess the sensitivity and specificity of miR expression for PDAC detection.

Results: Expression of EV-miR-21, EV-miR-25 and EV-miR-16 were increased in cases vs controls in PJ, while only EV-miR-210 was increased in serum. The potential to detect PC was good for a combination of PJ EV-miR-21, EV-miR-25, EV-miR-16 and serum miR-210, CA-19-9, with an area under the curve of 0.91, a specificity of 84.2% and a sensitivity of 81.5%.

Conclusion: Detection of miRNA from EVs in PJ is feasible. A combined panel of PJ EV-miR-21, EV-miR-25, EV-miR-16, and serum EV-miR-210 and CA19-9 distinguishes cases with PDAC from controls undergoing surveillance with a specificity of 81.5% and sensitivity of 84.2%.

Keywords: Biomarkers; Diagnosis; Endoscopic ultrasound; Extracellular vesicles; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic juice; Surveillance cohort; microRNA.