Dehqanzada Zia A, Storrer Catherine E, Hueman Matthew T, Foley Rebecca J, Harris Katie A, Jama Yusuf H, Shriver Craig D, Ponniah Sathibalan, Peoples George E
National Naval Medical Center, Henry M. Jackson Foundation, Bethesda, MD 20889, USA.
Oncol Rep. 2007 Mar;17(3):687-94.
We used the Luminex assay to compare serum cytokine profiles of breast cancer patients (BCa) to healthy controls, node-positive (NP) patients to node-negative (NN), and pre- and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine. Sera from 36 pre- and post-vaccination BCa, (12 NP and 24 NN) and 13 healthy, female donors, were evaluated using Luminex technology. Levels of 22 cytokines consisting of interleukin (IL)-1alpha, -1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -15, -17, IFN-gamma, G-CSF, GM-CSF, TNF-alpha, IP-10, MIP-1alpha, RANTES, eotaxin and monocyte chemotactic protein-1 (MCP-1) were assessed. Six of 22 cytokines showed significant differences between BCa and healthy controls. MCP-1, eotaxin, RANTES and GM-CSF levels were significantly elevated in BCa (P<0.009) and IL-1alpha and IL-4 levels were significantly decreased in BCa (P<0.015). Cytokine levels were generally elevated in NN patients compared to NP patients with the exception of eotaxin and IL-13, which were increased in NP patients. Three cytokines, IL-6, MIP-1alpha and G-CSF reached statistical significance (P<0.05). In 34 vaccinated BCa, MCP-1, eotaxin and IL-13 were significantly elevated post-vaccination with MCP-1 demonstrating the most significant response (median, 145.8-217.0 pg/ml, P=0.003). Using a multiplex assay we found significant differences in cytokine levels in sera of BCa compared to healthy controls, in NN compared to NP patients, and in vaccinated patients. Our results support an extended analysis of serum cytokine profiles for the potential development of predictive panels in diagnosis, staging and monitoring cancer vaccine trials.
我们使用Luminex检测法比较了乳腺癌患者（BCa）与健康对照者、淋巴结阳性（NP）患者与淋巴结阴性（NN）患者的血清细胞因子谱，以及接种HER2/neu E75肽疫苗的BCa患者接种疫苗前后的血清细胞因子谱。使用Luminex技术评估了36例接种疫苗前后的BCa患者（12例NP和24例NN）以及13名健康女性捐赠者的血清。检测了包括白细胞介素（IL）-1α、-1β、-2、-4、-5、-6、-7、-8、-10、-12、-13、-15、-17、干扰素-γ、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子-α（TNF-α）、干扰素诱导蛋白10（IP-10）、巨噬细胞炎性蛋白-1α（MIP-1α）、调节激活正常T细胞表达和分泌因子（RANTES）、嗜酸性粒细胞趋化因子和单核细胞趋化蛋白-1（MCP-1）在内的22种细胞因子的水平。22种细胞因子中有6种在BCa患者与健康对照者之间存在显著差异。BCa患者中MCP-1、嗜酸性粒细胞趋化因子、RANTES和GM-CSF水平显著升高（P<0.009），而IL-1α和IL-4水平显著降低（P<0.015）。与NP患者相比，NN患者的细胞因子水平总体升高，但嗜酸性粒细胞趋化因子和IL-13除外，这两种细胞因子在NP患者中升高。三种细胞因子，即IL-6、MIP-1α和G-CSF达到统计学显著性（P<0.05）。在34例接种疫苗的BCa患者中，接种疫苗后MCP-1、嗜酸性粒细胞趋化因子和IL-13显著升高，其中MCP-1的反应最为显著（中位数，145.8 - 217.0 pg/ml，P = 0.003）。通过多重检测，我们发现BCa患者血清中的细胞因子水平与健康对照者相比、NN患者与NP患者相比以及接种疫苗患者之间存在显著差异。我们的结果支持对血清细胞因子谱进行扩展分析，以用于癌症疫苗试验的诊断、分期和监测中预测指标的潜在开发。
