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.
Background. The influence of HLA class I and II loci on the susceptibility to melanoma remains an area of intense debate. This study aimed to examine whether the HLA system was related to melanoma susceptibility and prognosis in a southern Spanish population. Methods. In this study, HLA class I and class II genotyping were performed using polymerase chain reaction sequence-specific oligonucleotides (PCR-SSO) in 237 Spanish melanoma patients and 636 ethnically matched controls. Data were analyzed according to the clinical characteristics of the defined subgroups. Results. Compared to the control group, DRB1 ∗ 16:01 (4% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 3.28) and DQB1 ∗ 05:02 (4.9% vs. 2%, p = 0.001 , Pc = 0.017, OR = 2.54) were positivity associated with the susceptibility to melanoma. Both DRB1 ∗ 16:01 (5.4% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 4.46) and DQB1 ∗ 05:02 (6.5% vs. 2%, p = 0.001 , Pc = 0.017, OR = 3.44) also showed a positive correlation with Breslow thickness >1.5 mm, most notably at an early age of diagnosis (≤58 years), DRB1 ∗ 16:01 (4.2% vs. 1.3%, p = 0.001 , Pc = 0.035, OR = 3.41) and DQB1 ∗ 05:02 (5.4% vs. 2%, p = 0.002 , Pc = 0.034, OR = 2.86). Conclusion. These findings established HLA-DRB1 ∗ 16:01 and HLA-DQB1 ∗ 05:02 loci as melanoma risk factors in the southern Spanish population.
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