Early detection of head and neck cancer: Development of a novel screening tool using multiplexed immunobead-based biomarker profiling
Early detection of head and neck cancer: Development of a novel screening tool using multiplexed immunobead-based biomarker profiling
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DOI：
10.1158/1055-9965.epi-06-0602
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发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Ferris, Robert L.
中科院分区：
文献类型：
--
作者：
Linkov, Faina;Lisovich, Alex;Ferris, Robert L.
头颈部鳞状细胞癌（SCCHN）是一种侵袭性疾病，与免疫、炎症和血管生成反应的改变有关。更好地理解这些异常反应可能会改善SCCHN的早期检测和预后，并提供新的治疗靶点。先前的研究在小队列或SCCHN血清中检测了多重血清生物标志物的作用。我们假设一个由多种细胞因子、趋化因子、生长因子和其他肿瘤标志物组成的扩展组合，如果联合使用，可能会提供更高的诊断能力，这些标志物单独使用时可能与疾病状态显示出一些有希望的相关性。因此，我们评估了一种新型的多分析物LabMAP分析技术，该技术允许同时测量多种血清生物标志物。在116例治疗前的SCCHN患者（活动性疾病组）、103例成功治疗的患者（无疾病证据组）和117例无癌症证据的吸烟者对照的血清中测量了60种细胞因子、生长因子和肿瘤抗原的浓度。提供最高诊断能力的多标志物组合由25种生物标志物组成，包括表皮生长因子、表皮生长因子受体、白细胞介素（IL）-8、组织型纤溶酶原激活物抑制剂-1、甲胎蛋白、基质金属蛋白酶-2、基质金属蛋白酶-3、干扰素-α、干扰素-γ、干扰素诱导蛋白-10、活化调节的正常T细胞表达和分泌因子（RANTES）、巨噬细胞炎症蛋白-1α、IL-7、IL-17、IL-1受体-α、IL-2受体、粒细胞集落刺激因子、间皮素、胰岛素样生长因子结合蛋白1、E-选择素、细胞角蛋白-19、血管细胞粘附分子和癌抗原-125。使用ADE算法进行的统计分析得出敏感性为84.5%，特异性为98%，在交叉验证血清组中，活动性疾病组92%的患者被正确分类。所呈现的数据表明，使用多重血清生物标志物组合进行同时检测可能为头颈部癌症的早期检测提供一种有希望的新方法。
Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease that has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients before treatment (active disease group), 103 patients who were successfully treated (no evidence of disease group), and 117 smoker controls without evidence of cancer. The multimarker panel offering the highest diagnostic power was comprised of 25 biomarkers, including epidermal growth factor, epidermal growth factor receptor, interleukin (IL)-8, tissue plasminogen activator inhibitor-1, alpha-fetoprotein, matrix metalloproteinase-2, matrix metalloproteinase-3, IFN-alpha, IFN-gamma, IFN-inducible protein-10, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-let, IL-7, IL-17, IL-1 receptor-alpha, IL-2 receptor, granulocyte colony-stimulating factor, mesothelin, insulin-like growth factor binding protein 1, E-selectin, cytokeratin-19, vascular cell adhesion molecule, and cancer antigen-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%. specificity of 98%, and 92% of patients in the active disease group correctly classified from a cross-validation serum set. The data presented show that simultaneous testing using a multiplexed panel of serum biomarkers may present a promising new approach for the early detection of head and neck cancer.