Exosomal RNA biomarkers in pancreatic ductal adenocarcinoma: Systematic review and meta-analysis

Pancreatic cancer is a highly lethal malignancy, ranking tenth in incidence among all cancers and standing as the fourth leading cause of cancer-related mortality worldwide. This systematic review and meta-analysis evaluated the diagnostic performance of exosomal biomarkers for detecting pancreatic ductal adenocarcinoma (PDAC). A total of 1,666 records were identified through comprehensive searches in Scopus, Web of Science, and PubMed. After removing duplicates and screening titles, abstracts, and full texts, 15 studies comprising 1,961 individuals (971 PDAC patients and 990 controls) were included. The quality of studies was assessed using the QUADAS-2 tool, revealing potential biases mainly in patient selection and index test domains. Three biomarker categories were analyzed: exosomal microRNAs (exomiRs), cancer antigen 19-9 (CA 19-9), and glypican-1 (GPC1). ExomiRs demonstrated the highest pooled sensitivity (0.86; 95 % CI: 0.80-0.90) and lowest negative likelihood ratio (0.16; 95 % CI: 0.11-0.24), while CA 19-9 showed the highest specificity (0.91; 95 % CI: 0.84-0.95) and positive likelihood ratio (8.5; 95 % CI: 4.4-16.4). ExomiRs also had the highest diagnostic odds ratio (DOR = 35.4; 95 % CI: 18.7-67.0) and area under the SROC curve (AUC = 0.92; 95 % CI: 0.89-0.94), indicating superior diagnostic performance compared to CA 19-9 and GPC1 (AUC = 0.88 and 0.78, respectively). GPC1 consistently showed lower diagnostic metrics across all analyses. Deeks' funnel plot suggested no publication bias for CA 19-9 and GPC1, but indicated potential bias for exomiRs (P = 0.01). Overall, exomiRs appear to be promising non-invasive biomarkers for the early detection of PDAC, outperforming traditional and other exosome-based markers in diagnostic accuracy.