Nuclear factor-κB-related serum factors as longitudinal biomarkers of response and survival in advanced oropharyngeal carcinoma
Nuclear factor-κB-related serum factors as longitudinal biomarkers of response and survival in advanced oropharyngeal carcinoma
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DOI：
10.1158/1078-0432.ccr-06-3047
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发表时间：
2007-06-01
影响因子：
11.5
通讯作者：
Van Wales, Carter
中科院分区：
文献类型：
--
作者：
Allen, Clint;Duffy, Sonia;Van Wales, Carter
目的：在晚期癌症（包括头颈部鳞状细胞癌（SCC））患者的血清中可检测到由转录因子核因子-kappa B调节并由肿瘤和基质细胞分泌的细胞因子和生长因子。这些血清因子的纵向变化可能是治疗反应和存活的早期生物标志物。白细胞介素（IL）-6，IL-8，生长相关癌基因-1（GRO-1），血管内皮生长因子（VEGF），肝细胞生长因子（HGF）在对30名局部性高血压患者的前瞻性研究中，使用基线和每3个月获得的血清，通过Luminex多重测定法测定浓度。晚期（III/IV期）口咽鳞状细胞癌接受放化疗。通过考克斯比例风险模型和Kaplan-Meier生存分析确定基线和单个和多种细胞因子变化方向与病因特异性和无病生存期之间的关系。统计学分析包括调整吸烟状况和对放化疗的反应。结果：三年病因特异性和无病生存率分别为74.4%和68.9%。非吸烟史（P = 0.05）和较高的基线VEGF（P = 0.003）与生存率增加相关。调整吸烟史后，个体因素水平的纵向增加预测了病因特异性生存率的降低[IL-6：相对危险度（RR），3.8; 95%置信区间（95% CI），2.0-7.4; P = 0.004; IL-8：RR，1.6; 95% CI，1.2-2.2; P = 0.05; VEGF：RR，3.0; 95% CI，1.6-5.6; P = 0.01; HGF：RR，2.9; 95% CI，1.9-4.4; P = 0.02; GRO-1：RR，1.2; 95% CI，1.1-1.3; P = 0.02]。对于一个给定的个体，任何三个或更多因素的上四分位数的大幅增加与两个或更少因素水平大幅增加的患者相比，预测了更差的病因特异性生存率（P = 0.004）。治疗前VEGF水平和IL-6，IL-8，VEGF，HGF，和GRO-1可能是有用的生物标志物的反应和生存的局部晚期口咽和头颈部鳞状细胞癌患者的放化疗治疗。
Purpose: Cytokines and growth factors modulated by transcription factor nuclear factor-kappa B and secreted by tumor and stromal cells are detectable in serum of patients with advanced cancers, including head and neck squamous cell carcinomas (SCC). Longitudinal changes in these serum factors could be early biomarkers of treatment response and survival.Experimental Design: Interleukin (IL)-6, IL-8, growth-related oncogene-1 (GRO-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) concentrations were determined by Luminex multiplex assay using serum obtained at baseline and every 3 months in a prospective study of 30 patients with locally advanced (stage III/IV) oropharyngeal SCC receiving chemoradiation therapy. The relationship between baseline and direction of change in individual and multiple cytokines with cause-specific and disease-free survival was determined by Cox proportional hazards models and Kaplan-Meier survival analysis. Statistical analyses included adjustment for smoking status and response to chemoradiation.Results: Three-year cause-specific and disease-free survival was 74.4% and 68.9%. Nonsmoking history (P = 0.05) and higher baseline VEGF (P = 0.003) correlated with increased survival. Longitudinal increases in levels of individual factors predicted decreased cause-specific survival when adjusted for smoking history [IL-6: relative risk (RR), 3.8; 95% confidence interval (95% CI), 2.0-7.4; P = 0.004; IL-8: RR, 1.6; 95% Cl, 1.2-2.2; P = 0.05; VEGF: RR, 3.0; 95% Cl, 1.6-5.6; P = 0.01; HGF: RR, 2.9; 95% Cl, 1.9-4.4; P = 0.02; and GRO-1: RR, 1.2; 95% Cl, 1.1-1.3; P = 0.02]. For a given individual, large increases in the upper quartile for any three or more factors predicted poorer cause-specific survival compared with patients with two or fewer large increases in factor levels (P = 0.004).Conclusions: Pretreatment VEGF levels and longitudinal change in IL-6, IL-8, VEGF, HGF, and GRO-1 may be useful as biomarkers for response and survival in patients with locally advanced oropharyngeal and head and neck SCC treated with chemoradiation.