Increased circulating vascular endothelial growth factor in acute myeloid leukemia patients: a systematic review and meta-analysis

Background Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current studies have found that VEGF plays an important role in hematologic diseases including acute myeloid leukemia (AML). However, the circulating levels of VEGF in AML were still controversial among published studies. Methods Three databases including PubMed, EMBASE, and Cochrane Library databases were searched up to February 2020. All articles included in the meta-analysis met our inclusion and exclusion criteria. Studies will be screened and data extracted by two independent investigators. The Newcastle-Ottawa Scale (NOS) and the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool were applied to evaluate the quality of the included studies. A random-effects model was applied to pool the standardized mean difference (SMD). Heterogeneity test was performed by the Q statistic and quantified using I-2. All statistical analysis was conducted in Stata 12.0 software. Results Fourteen case-control studies were finally included in this systematic review and meta-analysis. Heterogeneity was high in our included studies (I-2 = 91.1%, P < 0.001). Sensitivity analysis showed no significant change when any one study was excluded using random-effect methods (P > 0.05). Egger's linear regression test showed that no publication bias existed (P > 0.05). Patients with AML, mainly those newly diagnosed and untreated, have higher VEGF levels (SMD = 0.85, 95% CI 0.28-1.42). Moreover, AML patients in n >= 40 group, plasma group, Asia and Africa group, and age >= 45 group had higher circulating VEGF levels (all P < 0.05). Conclusions Compared to healthy controls, our meta-analysis shows a significantly higher level of circulating VEGF in AML patients, and it is associated with sample size, sample type, region, and age.