Abstract
Purpose Previous studies have shown that melanoma cells produce excessive levels of cytokines, which have various biological roles during melanoma development. The aim of this study was to expand the profile of serum cytokines, chemokines, growth factors, and angiogenic factors that are associated with melanoma, to find more cytokines with abnormal concentrations in melanoma patients, to identify whether the level of cytokines correlated with prognostic variants, such as Breslow thickness and BRAF mutation, and, finally, to find out the cytokines that play important roles during melanoma development. Materials and Methods Multiplex immunobead assay technology and 45-plex immunoassays ProcartaPlex™ kits were used to simultaneously compare the levels of cytokines, growth factors, angiogenic factors, and chemokines between the serum of healthy patients (n = 30) and those with melanoma (n = 72). Data were analyzed according to the clinical characteristics of the designated patient subgroups. Results Compared to the control group, melanoma patients had higher levels of VEGF-A, PDGF-BB, IL-1RA, PIGF-1, IFN-γ, TNF-α, MIP-1α, and SCF, but lower levels of BDNF, SDF-1α, MCP-1, Eotaxin, EGF, and IL-7. Furthermore, the levels of TNF-α (P=0.320, r = 0.019), IFN-γ (P=0.311, r = 0.023), VEGF-A (P=0.014, r = 0.337), and BDNF (0.004, r = −0.391) showed a significant correlation with Breslow thickness. IL-7 was of lower levels in patients harboring BRAF mutants. Melanoma patients with high levels of MIP-1α and MCP-1 showed the poorest overall survival. Conclusions We found that the levels of VEGF-A and PDGF-BB in the serum of both primary and metastatic melanoma patients are elevated. TNF-α, IFN-γ, and VEGF-A presented a positive correlation with Breslow thickness, whereas BDNF showed a negative association. MIP-1α and MCP-1 correlated negatively with survival. In addition, lower levels of IL-7 were found in patients harboring BRAF mutants. These findings indicate that these cytokines may play critical roles in the progression of melanoma.
Highlights
Melanoma is a potentially lethal malignancy that occurs when melanocytes undergo DNA damage in response to ultraviolet light (UVB, UVC) [1]
Lower concentrations of BDNF, SDF-1α, MCP-1, Eotaxin, EGF, and IL-7 were observed in the serum of melanoma patients compared to healthy controls (Figure 1, Table 3)
IL-1RA, PIGF-1, IFN-c, and TNF-α levels were significantly elevated in primary melanoma and metastatic melanoma patients compared to healthy donors but showed no differences between primary melanoma and metastatic melanoma
Summary
Melanoma is a potentially lethal malignancy that occurs when melanocytes undergo DNA damage in response to ultraviolet light (UVB, UVC) [1]. Melanomas are prone to chemotherapy and radiotherapy resistance, leading to a poor prognosis. Studies have highlighted that the alteration of the cytokine levels in melanoma patients can affect the disease progression, response to the therapeutic, and the outcome of the disease [6, 7]. High concentrations of IL-10 are observed in patients with Stage II and IV melanomas and contribute to the downmodulation of antitumor responses [11], while abnormally high concentrations of IL-6 are associated with a poor response and outcome and contribute to the development and progression of early-stage melanoma [12,13,14]. E expression level of vascular endothelial growth factor (VEGF) presents a negative association with outcomes in patients with mucosal melanoma [15]. It is important to find out the critical cytokines that contribute to tumor progression for a better understanding of the process of tumor invasion and metastasis to get better results of antitumor chemotherapy and immunotherapy
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