Prognostic Impact of Expression of Bcl-2 and Bax Genes in Circulating Immune Cells Derived from Patients with Head and Neck Carcinoma
Prognostic Impact of Expression of Bcl-2 and Bax Genes in Circulating Immune Cells Derived from Patients with Head and Neck Carcinoma
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DOI：
10.1593/neo.121528
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发表时间：
2013-03-01
期刊：
影响因子：
4.8
通讯作者：
Hamakawa, Hiroyuki
中科院分区：
文献类型：
--
作者：
Tano, Tomoyuki;Okamoto, Masato;Hamakawa, Hiroyuki
在恶性肿瘤患者中，宿主免疫系统的抗肿瘤功能经常受到损害。在本研究中，我们评估了抗凋亡蛋白Bcl-2和促凋亡蛋白Bax（Bcl-2/Bax比值）在外周血单个核细胞中的mRNA表达比例与头颈部癌患者临床结局之间的关系。Bcl-2/Bax比值>= 1.2的患者的总生存期（OS）时间倾向于长于Bcl-2/Bax比值< 1.2的患者，但差异不显著（P = 0.084，n = 61）。Bcl-2/Bax比值= 1.2的患者的无病生存期（DFS）在统计学上显著长于Bcl-2/Bax比值< 1.2的患者（P = 0.001，n = 76）。所有Bcl-2/Bax比值= 2.0的患者在36个月后存活，并且存活24个月没有任何疾病迹象（Bcl-2/Bax >= 2.0对比Bcl-2/Bax < 2.0; P = 0.035，在OS中n = 61; P <0.001，在DFS中n = 76）。在56名接受UFT和OK-432联合放疗的免疫放化疗患者中，观察到Bcl-2/Bax比值与使用实体瘤疗效评价标准估计的疗效之间存在统计学显著性关系，以及与干扰素-γ的关系IFN-γ（+）与IFN-γ（-）诱导对治疗的反应[完全反应与部分反应+稳定疾病P = 0.002; IFN-γ（+）与IFN-γ（-）P = 0.046]。Bcl-2/Bax比值与CD 4 + T细胞绝对数、CD 4 + T细胞比率及NK细胞活性均呈显著相关。这些发现强烈地表明，Bcl-2和Bax基因在循环免疫细胞中的表达的平衡在头颈癌患者中具有高的预后价值。
Antitumor functions of the host immune system are frequently compromised in patients with malignancies. In the current study, we evaluated the relationship between expression ratio of mRNAs for the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax (the Bcl-2/Bax ratio) in peripheral blood mononuclear cells and clinical outcomes in patients with head and neck carcinomas. The overall survival (OS) time of patients with Bcl-2/Bax ratios >= 1.2 tended to be longer than that of patients with Bcl-2/Bax ratios < 1.2 but not significantly so (P = .084, n = 61). Disease-free survival (DFS) of patients with Bcl-2/Bax ratios = 1.2 was statistically significantly longer than that of patients with Bcl-2/Bax ratios < 1.2 (P = .001, n = 76). All of the patients whose Bcl-2/Bax ratio is = 2.0 were alive after 36 months and survived without any evidence of disease for 24 months (Bcl-2/Bax >= 2.0 versus Bcl-2/Bax < 2.0; P = .035, n = 61 inOS, P < .001, n = 76 in DFS, respectively). In 56 patients who received immunochemoradiotherapy using UFT and OK-432 in combination with radiotherapy, a statistically significant relationship between the Bcl-2/Bax ratio and the therapeutic effect estimated using Response Evaluation Criteria in Solid Tumors was observed, as well as a relation with interferon-gamma (IFN-gamma) induction in response to the therapy [P = .002 in complete response versus partial response + stable disease; P = .046 in IFN-gamma(+) versus IFN-gamma(-)]. Inaddition, there were significant correlations of the Bcl-2/Bax ratiowith both the absolute number of CD4(+) T cells and the rate of CD4+ T cell and natural killer cell activity. These findings strongly suggest that the balance of expression of Bcl-2 and Bax genes in circulating immune cells has a high prognostic value in head and neck cancer patients.