Plasma small extracellular vesicle microRNAs as non-invasive biomarkers for the diagnosis of pancreatic ductal adenocarcinoma.

Abstract

4227 Background: Current non-invasive approaches for the diagnosis of pancreatic ductal adenocarcinoma (PDAC) exhibit inherent limitations in accuracy. Consequently, there exists an urgent and unmet need for novel non-invasive biomarkers exhibiting high sensitivity and specificity to enable PDAC diagnosis. Methods: We employed small RNA sequencing to detect microRNA (miRNA) expression in small extracellular vesicles (sEVs) isolated from plasma samples of study participants (n = 208). A diagnostic model was developed (n = 140) and validated (n = 68) to discriminate between patients with PDAC and non-malignant controls (healthy individuals, chronic pancreatitis, intraductal papillary mucinous neoplasms, serous cystadenomas, solid pseudopapillary tumors, pancreatic cysts, and pancreatic abscesses). Results: The small RNA sequencing analysis of plasma sEV miRNA identified 32 differentially expressed sEV miRNAs between non-malignant controls and PDAC patients. The diagnostic model with the best performance was constructed using 17 sEV miRNAs. The diagnostic model achieved an area under curve (AUC) of 0.939, a sensitivity of 93%, and a specificity of 90% in the training cohort and an AUC of 0.951, a sensitivity of 95%, and a specificity of 83% in the test cohort. We identified the distinct characteristics of plasma sEV miRNAs among non-malignant controls compared to PDAC patients. Moreover, nine negative miRNAs and one positive miRNA were found significantly associated with the death risk of PDAC (all p < 0.05). Conclusions: Our findings demonstrates that plasma sEV miRNA exhibits a highly discriminative biomarker for distinguishing non-malignant group from malignant group, making it a promising tool for the diagnosis of PDAC.