Systematic review and meta-analysis: diagnostic accuracy of exosomes in pancreatic cancer

Early, non-invasive identification can generally enhance the survival rate for asymptomatic pancreatic cancer (PC). This systematic review and meta-analysis is conducted to evaluate the precision of diagnosing PC using serum and duodenal fluid exosomes.

Following the guidelines of PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses), searches were conducted in the PubMed, Embase, Cochrane Library, and Web of Science databases in April 2024. A study was considered appropriate if it provided diagnostic precision and accuracy for patients with pancreatic cancer. The combined diagnostic impact was assessed by calculating the area beneath the aggregated SROC curve, and the quality of the studies included was evaluated using the QUADAS-2 checklist. All statistical evaluations and graphical representations utilized STATA 14.0.

Employing the terms "exosomes" and "pancreatic cancer" along with the search methodology, research was conducted across PubMed, Web of Science, Cochrane, and Embase databases. A total of 1202 studies were extracted from the databases, out of which nine were ultimately selected based on specific inclusion and exclusion standards. Across eight studies, exosomes were isolated from serum, while in a different one, they were taken from duodenal fluid. This document conducts subgroup analyses focusing on various types of exosome biomarkers, their origins, isolation techniques, and methods for analyzing biomarkers. Within the subset of exosome biomarker types, the group with exosomal cell surface proteoglycan exhibited the greatest combined sensitivity (0.96 (95% CI = 0.81-0.99) and specificity (0.90 (95% CI = 0.83-0.95)). Additionally, the set of exosomal cell surface proteoglycans showed the highest aggregated diagnostic ratio (215.92), combined positive likelihood ratio (9.96), area under the curve (0.93), and kombiniertes negative Likelihood-Ratio (0.05). The combined sensitivity of serum-derived exosomes stood at (0.86 (95% CI = 0.77-0.92)), the collective specificity at (0.83 (95% CI = 0.77-0.89)), the aggregate positive likelihood ratio at (5.22), the combined diagnostic ratio at (31.48), the overall area beneath the curve at (0.91), and the combined negative likelihood ratio at (0.17). Within the subgroup examination of exosome isolation techniques, ultracentrifugation emerged as the most sensitive method (0.90 (95% CI = 0.74-0.97)), the most specific method (0.89 (95% CI = 0.83-0.93)), the top positive likelihood ratio (8.35), the highest diagnostic ratio (76.48), the largest combined curve area (0.92), and the smallest negative likelihood ratio (0.11) in the aggregated data. Within the subset of biomarker analysis methods, the aggregate sensitivity via qRT-PCR was (0.84 (95% CI = 0.74-0.90)), the collective specificity (0.78 (95% CI = 0.64-0.87)), the aggregate diagnostic ratio (18.11), the aggregate area under the curve (0.88), the aggregate positive likelihood ratio (3.77), and the combined negative likelihood ratio (0.21).

Overall, exosomes are still valuable in the diagnosis of pancreatic cancer. In subgroup analyses, the proteoglycan found on exosomal cell surfaces is highly valuable for diagnosing pancreatic cancer. The more frequent separation method used in the nine included studies was ultracentrifugation, and it did demonstrate good data. Nonetheless, to verify their practicality and usefulness in clinical environments, a significant amount of clinical trials are still necessary.