Proteomic analysis of head & neck squamous cell cancer

头颈部鳞状细胞癌(HNSCC)是全球第五大最常见的恶性肿瘤，是一种 MAJ或国际健康问题。这些肿瘤构成了一个解剖异质性的肿瘤群。 来自口腔、口咽、下咽、喉和鼻咽。虽然所有人都有共同的病因 与烟草和/或酒精暴露有关，起源于这些不同部位的肿瘤可以表现出不同的 通过原发肿瘤的组织病理学无法预测，但通过基因图谱可以发现的行为。因此，基因 使用复杂的EDNA微阵列和全球蛋白质组分析对原发肿瘤进行表达谱分析将有可能 产生预测侵袭性生长、转移潜能和对几种治疗类型的反应性的信息。 这项拟议研究的长期目标是使用原代HNSCC的蛋白质组学分析来识别将 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， 晚期HNSCC综合治疗效果有限。因此，可以预测肿瘤行为的新诊断方法 包括对治疗的反应将产生很高的临床影响。我们在拟议的研究中的目标是确定具体的 预测HNSCC肿瘤行为和患者预后的蛋白质组变化，并开发新的、简单的 诊断性测试将加强患者护理并改善临床结果。R21可行性的具体目标 阶段为：1-检测蛋白质提取和LC-MS分析的可靠性。使用随机效应模型，可靠性 并计算出测量的标准误差，以置信度较低的可靠性为判断标准 &gt；90%的边界。2-检验LC-MS分析用于HNSCC鉴别/分类的可行性 临床状态。以目标1的可信度分数为界的目标多肽将用于标准的统计判别 对数据进行分析和监督聚类，以识别单个目标或一组目标多肽 区分不同临床上与生存相关的样本，如分期、复发和转移潜能。这个 R33阶段的具体目标将：-1-通过分析HNSCC扩大全球蛋白质组和临床数据收集 从三个解剖部位产生总共135个样本；2-识别和表征区分生物的多肽 可变性；以及3-启动新诊断测试的开发。

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.