Elevated VEGF-A & PLGF concentration in aqueous humor of patients with uveal melanoma following Iodine-125 plaque radiotherapy

AIM: To measure the concentration of vascular endothelial growth factor-A(VEGF-A), and placental growth factor(PLGF) in aqueous humor of uveal melanoma patients before and after Iodine-125 plaque therapy(IPT), determine the postoperative fluctuation and evaluate associated factors in vivo.METHODS: Participants were 18 Chinese patients with uveal melanoma who were elected to IPT. Undiluted aqueous humor samples were collected at Iodine plaque implant and removal time, then stored immediately at-80℃ until assayed. The concentration of VEGF-A, PLGF and other 7 cytokines comprising interleukin-2(IL-2), IL-8, IL-10, interferon(IFN)-γ, programmed death(PD)-1, transforming growth factor(TGF)-β1 and insulin-like growth factor(IGF)-1 in aqueous humor was measured using Raybiotech immunoassay kit, a high throughput strategy. The VEGF-A and PLGF levels were compared across preoperation and postoperation subgroups, as well as those of other 7 interleukins. Correlation and grouped analyses were conducted to determine the independent effects of clinical parameters and other cytokines on VEGF-A and PLGF concentration or fluctuation. This study set a self-control design.RESULTS: VEGF-A(P=0.038) and PLGF(P=0.026) were the only two increased cytokines after IPT. Preoperative and postoperative level of VEGF-A and PLGF(r=0.575, P=0.013;r=0.987, P<0.001) correlated with each other significantly. Level of VEGF-A(r=0.626, P=0.005;r=0.588, P=0.01) and PLGF(r=0.616, P=0.007;r=0.588, P=0.01) had positive correlation with tumor thickness consistently. Elevated VEGF-A or PLGF level were strong predictive factors of each other(P=0.007, OR=60.0). The elevated VEGF-A group showed a higher postoperative level of IFN-γ(P=0.005), IL-2(P<0.001) and IL-10(P=0.004) in aqueous humor. When the elevated PLGF group got similar results that a higher postoperative level of IFN-γ(P=0.007), IL-2(P<0.001) and IL-10(P=0.013) in aqueous humor. CONCLUSION: This study reveals that VEGF-A and PLGF in aqueous humor significantly increased with tumor thickness and radiation process in uveal melanoma patients. VEGF-A and PLGF may be crucial in uveal melanoma genesis and radiotherapy reactions. Immune mediators comprised IFN-γ, IL-2 and IL-10 could play roles in the link between inflammation and angiogenesis in uveal melanoma when exposed to radiotherapy.