Investigating Vitreous Cytokines in Choroidal Melanoma

Abstract

Due to the close relationship between the vitreous and posterior eye layers, the microenvironment of these layers can affect the composition of the vitreous. Molecular analysis of the vitreous may therefore provide important insights into the pathogenesis of chorioretinal diseases. In this study, vitreous cytokines (n = 41) were evaluated to gain further insights into the tumor microenvironment in uveal melanoma (UM) arising from the choroid (CM). Cytokine levels were measured using a bead-based multiplex immunoassay panel in vitreous samples obtained from 32 eyes, including 18 with CM and 14 controls. Median fluorescence intensity values were extracted and used as relative quantification of the cytokine abundance. Vitreous cytokine levels were compared between the CM and non-CM groups and between different prognostic categories within the CM group (classified as having low or high metastatic risk using tumor biopsy-based gene expression profiling). Correlations between vitreous cytokine levels and tumor dimensions were also evaluated. Our analysis revealed twenty-six vitreous cytokines significantly upregulated in CM-affected eyes compared to the control eyes. Within the CM group, six vitreous cytokines showed altered levels (five upregulated and one downregulated) in eyes with high- vs. low-risk tumors. Levels of these six plus several other cytokines showed correlations with the tumor dimensions. In conclusion, our study has uncovered several UM-relevant vitreous cytokines, worthy of follow-up in larger studies as potential candidates for liquid biopsy-based biomarker development and/or new therapeutic targeting.

Recent Advances in Molecular and Genetic Research on Uveal Melanoma

“…In addition, the vitreous humor of UM patients ( n = 8) with high-risk GEP tumors showed higher expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1), HGFR (hepatocyte growth factor receptor), PYGL (liver glycogen phosphorylase) and ENPP-2 (ectonucleotide pyrophosphatase/phosphodiesterase 2) proteins in comparison to controls ( n = 3) [ 115 ]. The analysis of cytokines ( n = 32) revealed that twenty-six were differentially expressed in the vitreous humor from UM patients compared to the control group [ 116 ]. Among these, five cytokines (PDGFAB/BB, G-CSF, MCP-3/CCL7, IL-13 and TNF-β) were found to be elevated in the group identified as high-risk of metastasis according to the GEP analysis [ 116 ].…”

“…The analysis of cytokines ( n = 32) revealed that twenty-six were differentially expressed in the vitreous humor from UM patients compared to the control group [ 116 ]. Among these, five cytokines (PDGFAB/BB, G-CSF, MCP-3/CCL7, IL-13 and TNF-β) were found to be elevated in the group identified as high-risk of metastasis according to the GEP analysis [ 116 ].…”