Blood Small Extracellular Vesicles Derived Mirnas To Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis

Background: The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined.Methods: In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients.Results: The linear model from the differentially expressed blood small EV miR-95-3p divided by miR-26b-5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19-9 (CA19-9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR-95-3p was associated with a "consequence" of "cancer" and miR-26b-5p as a "cause" of "pancreatitis." A subgroup analysis revealed that blood small EV miR-335-5p/miR-340-5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020).Conclusions: This study indicated that blood small EV miR-95-3p/miR-26b-5p and its combination with serum levels of CA19-9 could separate PDAC from CP, and miR-335-5p/miR-340-5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC.