Diagnostic value of various liquid biopsy methods for pancreatic cancer A systematic review and meta-analysis

Background: Liquid biopsy is a novel method for cancer diagnosis, which has been applied in lung and breast cancers, demonstrating high diagnostic value. However, clinical value of it in pancreatic cancer (PC) remains to be verified. The aim of this meta-analysis was to evaluate overall diagnostic value of various liquid biopsy methods (circulating tumor DNA, circulating tumor cells and exosomes) in detecting PC. Methods: We comprehensively searched relevant studies in PubMed, Medline, Embase, and Web of Science without time limitation according to PRISMA. Data necessary for reconstructing a 2 x 2 table was calculated from the original articles. The methodological quality of included studies was evaluated by QUADAS-2. Statistical analysis including was performed by the software Meta-Disc version 1.4, and STATA 14.2. Results: A total of 19 studies including 1872 individuals were included in this meta-analysis. In which, 7 were studies about ctDNA, 7 were on CTCs and 6 were about exosomes (Sefrioui D-1, studied diagnostic accuracy of both ctDNA and CTCs, with no common patients in these 2 groups). The pooled sensitivity estimates for ctDNA, CTCs and exosomes in detecting PC with their 95% confidential intervals (95% CI) were 0.64 (95%CI 0.58-0.70), 0.74 (95%CI 0.68-0.79) and 0.93 (95%CI 0.90-0.95), respectively. The pooled specificity estimates were 0.92(95%CI 0.88-0.95), 0.83 (95%CI 0.78-0.88) and 0.92 (95%CI 0.88-0.95), respectively. The area under curve (AUC) of the sROC for ctDNA, CTCs and exosomes in detecting PC were 0.9478, 0.8166, and 0.9819, respectively. The overall sensitivity, specificity and AUC of the sROC curve for overall liquid biopsy in detecting PC were 0.80 (95%CI 0.77-0.82), 0.89 (95%CI 0.87-0.91) and 0.9478, respectively. Conclusion: This meta-analysis confirmed that liquid biopsy had high diagnostic value in detecting PC. In ctDNA, CTCs and exosomes these 3 subgroups, exosomes showed highest sensitivity and specificity.