Proteomic analysis of head & neck squamous cell cancer

描述（由申请人提供） 头颈部鳞状细胞癌（HNSCC）是全球第五大常见恶性肿瘤，代表了一个主要的国际健康问题。这些肿瘤构成了一组解剖学上异质的肿瘤，起源于口腔、口咽、下咽、喉和鼻咽。虽然所有这些肿瘤都与烟草和/或酒精暴露有共同的病因学关联，但起源于这些不同部位的肿瘤可以表现出不同的行为，这些行为不能通过原发性肿瘤的组织病理学预测，但可以通过基因分析识别。因此，使用复杂的eDNA微阵列和全球蛋白质组学分析的原发性肿瘤的基因表达谱将可能产生预测侵袭性生长、转移潜力和对几种类型的治疗的反应性的信息。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区分肿瘤类型的蛋白质，并用于预测肿瘤行为。 虽然手术可以治愈早期疾病，但综合治疗在晚期HINSCC中的成功率有限。因此，可以预测肿瘤行为（包括对治疗的反应）的新诊断将具有很高的临床影响。我们在拟议研究中的目标是确定蛋白质组中预测HNSCC中肿瘤行为和患者结局的特定变化，并开发新的，简单的诊断测试，以加强患者护理并改善临床结局。R21可行性阶段的具体目标是：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，将计算测量的可靠性和标准误，继续进行的标准是置信下限> 90%的可靠性。2-测试LC-MS分析可用于区分/分类具有不同临床状态的HNSCC的可行性。具有来自目标1的可靠性评分截止值的靶肽将用于标准统计区分分析和数据的监督聚类，以鉴定单个靶或靶肽组，其可区分具有各种存活临床相关性的样品，例如阶段复发，和转移潜能。R33阶段的具体目标是：1-扩大全球蛋白质组学和临床数据收集，分析来自三个解剖部位的HNSCC，共产生135个样本; 2-鉴定和表征区分生物变异性的肽; 3-启动新诊断测试的开发。

DESCRIPTION (provided by applicant) Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide, representing a major international health problem. These tumors constitute an anatomically heterogeneous group of neoplasms arising from the oral cavity, oropharynx, 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 discernable 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 HINSCC. 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 discriminate/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 peptides 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.