一项关于纵向血清细胞因子和血管生成因子水平作为头颈部鳞状细胞癌患者治疗反应和生存标志物的初步研究。

A pilot study of longitudinal serum cytokine and angiogenesis factor levels as markers of therapeutic response and survival in patients with head and neck squamous cell carcinoma.

作者信息

Druzgal Colleen H, Chen Zhong, Yeh Ning T, Thomas Giovana R, Ondrey Frank G, Duffey Dianne C, Vilela Ronald J, Ende Kevin, McCullagh Linda, Rudy Susan F, Muir Christine, Herscher Laurie L, Morris John C, Albert Paul S, Van Waes Carter

机构信息

Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bldg. 10 CRC, Rm 4-2732, 10 Center Drive, Bethesda, MD 20892, USA.

出版信息

Head Neck. 2005 Sep;27(9):771-84. doi: 10.1002/hed.20246.

DOI:10.1002/hed.20246

PMID:15920746

Abstract

BACKGROUND

Head and neck squamous cell carcinomas (HNSCCs) were previously shown to express a repertoire of cytokines and angiogenesis factors that contribute to malignant pathogenesis and are detectable in serum. Pretreatment and posttreatment serum levels of cytokines and angiogenesis factors were evaluated as markers for outcome in patients with HNSCC.

METHODS

Baseline cytokine and factor levels of 29 patients with HNSCC were compared with those of 15 age-matched and sex-matched controls, and pretreatment and posttreatment levels of 22 of the patients eligible for treatment and followed for a median of 37 months were compared.

RESULTS

Mean serum concentrations of interleukin (IL)-6, IL-8, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and growth regulated oncogene 1 (GRO-1) were increased in patients with HNSCC, but elevation of these factors was not associated with clinical outcome. However, changes in first posttreatment serum cytokine levels were observed for many of the patients consistent with response, progression, and survival. Later increases in IL-6 or HGF were observed in patients who had a relapse and inflammatory or infectious complications. A relationship between the change in the pretreatment and first posttreatment cytokine measurement with survival was detected for HGF, IL-8, IL-6, and VEGF using a Cox-proportional hazards model (p = .004, p = .06, p = .10, and p = .11). The association between longitudinal decreases in IL-6, IL-8, VEGF, and HGF throughout the follow-up with survival was detected with a time-dependent Cox model (p = .01, .07, .08, and .05, respectively).

CONCLUSIONS

Longitudinal changes in serum HGF, IL-6, IL-8, and VEGF were detected with treatment response, relapse, or complications in individual patients and were associated with survival, with HGF showing the strongest relationship with survival. HGF, IL-6, IL-8, and VEGF merit investigation as markers of response, survival, and recurrence in larger prospective studies.

摘要

背景

先前研究表明，头颈部鳞状细胞癌（HNSCC）可表达一系列细胞因子和血管生成因子，这些因子有助于恶性肿瘤的发病机制，且可在血清中检测到。对HNSCC患者治疗前和治疗后血清中细胞因子和血管生成因子水平进行评估，作为预后指标。

方法

将29例HNSCC患者的基线细胞因子和因子水平与15例年龄和性别匹配的对照者进行比较，并对22例符合治疗条件且中位随访37个月的患者治疗前和治疗后的水平进行比较。

结果

HNSCC患者血清白细胞介素（IL）-6、IL-8、肝细胞生长因子（HGF）、血管内皮生长因子（VEGF）和生长调节致癌基因1（GRO-1）的平均浓度升高，但这些因子的升高与临床预后无关。然而，许多患者首次治疗后血清细胞因子水平的变化与反应、进展和生存情况一致。复发且伴有炎症或感染并发症的患者，后期IL-6或HGF水平升高。使用Cox比例风险模型检测到，治疗前和首次治疗后细胞因子测量值的变化与HGF、IL-8、IL-6和VEGF的生存之间存在相关性（p = .004、p = .06、p = .10和p = .11）。使用时间依赖性Cox模型检测到，随访期间IL-6、IL-8、VEGF和HGF的纵向下降与生存之间存在相关性（分别为p = .01、.07、.08和.05）。