Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma—a systematic review and meta-analysis

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive versus negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR=2.81, CI:1.31-6,00, I2=88.7%, p<0.001), and progression (UHR=3.33, CI: 2.33-4.77, I2=0, p=0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR=5.55, CI: 3.24-9.49, I2=0, p=0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR=2.51, CI: 0.55-11.43, I2=90.3%, p<0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR=4.08, CI: 2.16-7.69, I2=46.9%, p=0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.