Proteomic analysis of head & neck squamous cell cancer

头颈部鳞状细胞癌（HNSCC）是世界上第五大常见恶性肿瘤，代表了 重大国际健康问题。这些肿瘤构成了一组解剖学上异质的肿瘤， 从口腔、口咽、下咽、喉和鼻咽。虽然所有的都有一个共同的病因 与烟草和/或酒精暴露相关，起源于这些不同位置的肿瘤可以表现出不同的 原发性肿瘤的组织病理学无法预测，但通过基因分析可致病的行为。因此，基因 使用先进的eDNA微阵列和全球蛋白质组学分析原发性肿瘤的表达谱可能 产生的信息，将预测侵略性的增长，转移的潜力和反应的几种类型的治疗。 这项研究的长期目标是利用原发性HNSCC的蛋白质组学分析来鉴定蛋白质， 区分肿瘤类型并用于预测肿瘤行为。虽然手术可以治愈早期疾病， 综合疗法在晚期HNSCC中的成功有限。因此，新的诊断方法可以预测肿瘤的行为， 包括对治疗的反应将具有很高的临床影响。我们的目标是在拟议的研究是确定具体的 预测HNSCC中肿瘤行为和患者结局的蛋白质组变化，并开发新的，简单的 诊断测试，将加强病人护理和改善临床结果。R21可行性的具体目标 阶段是：1-测试蛋白质提取和LC-MS分析的可靠性。使用随机效应模型，可靠性 并计算测量的标准误差，继续进行的标准是具有较低置信度的可靠性 > 90%。2-测试LC-MS分析可用于区分/分类具有不同的HNSCC的可行性。 临床状态具有目标1的可靠性评分截止值的目标肽将用于标准统计区分 对数据进行分析和监督聚类以鉴定单个靶或靶肽组， 区分样本与生存的各种临床相关性，如阶段，复发和转移潜力。的 R33阶段的具体目标是：-1-通过分析HNSCC，扩大全球蛋白质组学和临床数据收集 从三个解剖部位产生总共135个样品; 2-鉴定和表征区分生物活性的肽， 可变性;和3-启动新的诊断测试的开发。

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide, representing a maj or international health problem. These tumors constitute an anatomically heterogeneous group of neoplasms arising from the oral cavity, oropharyrax, hypopharynx, larynx and nasopharynx. While all have in common an etiological association with tobacco and/or alcohol exposure, tumors originating from these different locations can exhibit varying behavior that is not predictable by histopathology of the primary tumor but is diseemable by gene profiling. Thus, gene expression profiling of primary tumors using sophisticated eDNA microarray and global proteomic analyses will likely yield information that will predict aggressive growth, metastatic potential and responsiveness to several types of therapy. The long-term goal of the proposed study is to use proteomic analysis of primary HNSCC to identify proteins that will differentiate tumor types and be used to predict tumor behavior. While surgery can cure early stage disease, multimodality therapy is of limited success in later stage HNSCC. Thus new diagnostics that can predict tumor behavior including response to therapy will have high clinical impact. Our goal in the proposed study is to identify specific changes in the proteome that predict tumor behavior and patient outcome in HNSCC, and to develop new, simple diagnostic tests that will enhance patient care and improve clinical outcome. The specific aims for the R21 feasibility phase are: 1- Test the reliability of protein extraction and of LC-MS analysis. Using a random effects model, reliability and standard error of measurement will be computed and the criterion for proceeding is reliability with lower confidence bound of>90%. 2- Test the feasibility that LC-MS analysis can be used to discrirm'nate/classify HNSCC with different clinical status. Target peptides with a reliability score cutoff from aim 1 will be used in standard statistical discrimination analysis and supervised clustering of the data to identify either single targets or groups of target pcptides than can discriminate samples with various clinical correlates of survival, such as stage, recurrence, and metastatic potential. The specific aims for the R33 phase will: -1- expand global proteomic and clinical data collection with analysis of HNSCC from three anatomic sites yielding a total of 135 samples; 2- identify and characterize peptides that discriminate biologic variability; and 3- initiate development of new diagnostic tests.