Extracellular vesicle biomarkers for pancreatic cancer diagnosis: a systematic review and meta-analysis

Abstract

Background Extracellular vesicle (EV) biomarkers have promising diagnosis and screening capacity for several cancers, but the diagnostic value for pancreatic cancer (PC) is controversial. The aim of our study was to review the diagnostic performance of EV biomarkers for PC. Methods We performed a systematic review of PubMed, Medline, and Web Of Science databases from inception to 18 Feb 2022. We identified studies reporting the diagnostic performance of EV biomarkers for PC and summarized the information of sensitivity, specificity, area under the curve (AUC), or receiver operator characteristic (ROC) curve) in according to a pre-designed data collection form. Pooled sensitivity and specificity was calculated using a random-effect model. Results We identified 39 studies, including 2037 PC patients and 1632 noncancerous, seven of which were conducted independent validation tests. Seventeen studies emphasized on EV RNAs, sixteen on EV proteins, and sixteen on biomarker panels. MiR-10b, miR-21, and GPC1 were the most frequently reported RNA and protein for PC diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 79% (95% CI: 77–81%) and 87% (95% CI: 85–89%), 72% (95% CI: 69–74%) and 77% (95% CI: 74–80%), respectively. the pooled sensitivity and specificity of EV RNA combined with protein panels were 84% (95% CI: 81–86%) and 89% (95% CI: 86–91%), respectively. Surprisingly, for early stage (stage I and II) PC EV biomarkers showed excellent diagnostic performance with the sensitivity of 90% (95% CI: 87–93%) and the specificity of 94% (95% CI: 92–95%). Both in sensitivity and subgroup analyses, we did not observe notable difference in pooled sensitivity and specificity. Studies might be limited by the isolation and detection techniques of EVs to a certain extent. Conclusions EV biomarkers showed appealing diagnostic preference for PC, especially for early stage PC. Solving the deficiency of technologies of isolation and detection EVs has important implications for application these novel noninvasive biomarkers in clinical practice.

Encoded Fusion-Mediated MicroRNA Signature Profiling of Tumor-Derived Extracellular Vesicles for Pancreatic Cancer Diagnosis

“…In addition, six types of pancreatic cancer-associated miRNAs , (miRNA-21, miRNA-16, miRNA-10b, miRNA-155, miRNA-1246, and miRNA-196a) were chosen as models to evaluate the capability of encoded fusion-mediated multiplex detection by a panel of ETFBs containing the corresponding MBs (Table S2). The specificity of these MBs was satisfactory (Figure S14).…”

“…Consistent with previous reports, the expression levels of these six types of tEVs-miRNAs were higher in pancreatic cancer patients than in healthy donors and pancreatitis patients. 8,40 Moreover, the diagnostic accuracy of the sum of six types tEV-miRNAs (98%) was higher than that of a single tEV-miRNA (73% for miRNA-155 as an example), indicating that multiplex detection has advantages in improving the diagnostic accuracy of pancreatic cancers (Figure 4D). Collectively, the ETFB-based encoded fusion strategy is a feasible tool for the clinical diagnosis of pancreatic cancer and can improve diagnostic accuracy due to its multiplex detection capability.…”

Cancer-Derived Extracellular Vesicles as Biomarkers for Cutaneous Squamous Cell Carcinoma: A Systematic Review

“…A study involving 139 patients with early stage pancreatic, ovarian, or bladder cancer demonstrated an area under the curve of 0.95 (sensitivity 71.2%, specificity 99.5%) using an extracellular vesicle protein-based diagnostic blood test [ 25 ]. A meta-analysis of 39 studies on pancreatic cancer concluded that EV RNAs were effective biomarkers for pancreatic cancer screening with 79% sensitivity and 87% specificity, even at its rudimental stage [ 52 ]. When combining both protein and RNA biomarkers, they came to an excellent diagnostic performance of 90% sensitivity and 94% specificity for stage I and II pancreatic cancer.…”

Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery

“…In systematic review reports, several markers have been labelled as promising, yet remain under investigation for clinical utility. Extracellular vesicle (including microRNAs and others) as biomarkers have been scrutinized, 60 yet technological difficulties and standardization needs to be overcome before translation into clinical use.…”