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，是一个重大的国际健康问题。这些肿瘤构成了一组解剖上不同的肿瘤，它们起源于口腔、口咽、下咽、喉和鼻咽。虽然所有这些肿瘤在病因上都与烟草和/或酒精暴露有关，但源自这些不同位置的肿瘤可以表现出不同的行为，这是原发肿瘤的组织病理学无法预测的，但通过基因图谱可以区分出来。因此，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基因表达谱分析，可能会产生预测侵袭性生长、转移潜力和对几种治疗类型的反应的信息。这项拟议研究的长期目标是使用原发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的蛋白质。虽然手术可以治愈早期疾病，但综合治疗对晚期HINSCC的疗效有限。因此，能够预测包括治疗反应在内的肿瘤行为的新诊断方法将具有很高的临床影响。在这项拟议的研究中，我们的目标是确定蛋白质组中预测HNSCC肿瘤行为和患者预后的特定变化，并开发新的、简单的诊断测试，以加强患者护理和改善临床结果。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。利用随机效应模型计算可靠性和测量标准误差，以可靠性为判断标准，其置信限为90%。2-测试LC-MS分析可用于区分/分类HNSCC的可行性，具有不同临床状态的HNSCC，目标肽将用于标准统计判别分析和数据的监督聚类，以识别单个目标或靶肽组，从而可以区分具有各种临床生存相关因素的样本，如阶段复发和转移潜力。R33阶段的具体目标将：1-扩大全球蛋白质组和临床数据收集，从三个解剖地点分析HNSCC，总共产生135个样本；2-识别和表征区分生物变异性的多肽；以及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.