Prognostic value of extracellular vesicles in colorectal cancer: a systematic review and meta-analysis

Objective Extracellular vesicles (EVs) are prognostic factors in colorectal cancer (CRC). This study aims to evaluate the prognostic value of EVs CRC. Methods Clinical studies that directly investigated the association between EVs in different kinds of body fluids of CRC patients and patient prognosis were included by searching the PubMed, Web of Science, ClinicalTrials, and CENTRAL databases. The associations between single biomarkers, molecular panels, and EVs count with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed. Heterogeneity was assessed using the I-2 statistic, with a random-effects model applied when I-2 > 30% and a fixed-effects model when I-2 <= 30%. Results A total of 56 studies involving 5,985 patients were included. All included studies detected EVs in blood. Univariate analysis revealed an association between EVs single-biomarkers and OS (pHR = 2.07, 95% CI: 1.73-2.73) and DFS (pHR = 2.20, 95% CI: 1.46-2.79). Additionally, univariate analysis revealed an association between molecular-panels in EVs and OS (pHR = 3.67, 95% CI: 2.51-5.36) and RFS (pHR = 3.97, 95% CI: 1.57-10.08). Moreover, an association was observed between a EVs count and OS (pHR = 1.87, 95% CI: 1.40-2.49). On the basis of the results of the meta-regression and subgroup analyses, the subgroups of EVs and the disease stage of CRC patients are key factors contributing to the heterogeneity in the associations between EVs single-biomarkers and OS. Conclusion This study provides compelling evidence that EVs from blood hold prognostic value in CRC.