Proteomic analysis of head & neck squamous cell cancer

头部蛋白质组学分析

• 批准号: 7682892
• 负责人: MICHAEL B PRYSTOWSKY
• 金额: $ 69.52万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-14 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7682892
• 关键词: Anatomic Sites; Behavior; Binding; Cell Line; Clinical; Clinical Data; Combined Modality Therapy; Data; Data Collection; Development; Diagnostic; Diagnostic tests; Discrimination; Disease; Distant; Exhibits; Future; Gene Expression Profiling; Genes; Goals; Growth; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Histopathology; Human; International Health Problems; Larynx; Location; Malignant Neoplasms; Malignant Squamous Cell Neoplasm; Measurement; Modeling; Nasopharynx; Neck; Neoplasm Metastasis; Neoplasms; Operative Surgical Procedures; Oral cavity; Oropharyngeal; Outcome; Patient Care; Patients; Peptides; Pharyngeal structure; Phase; Predictive Value; Primary Neoplasm; Proteins; Proteome; Proteomics; Recurrence; Sampling; Site; Staging; Testing; Time; Tobacco; Translating; alcohol exposure; cDNA Arrays; clinical practice; hypopharynx; improved; innovation; liquid chromatography mass spectrometry; novel diagnostics; prognostic; programs; response; success; tongue sampling; tool; tumor

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.

头颈鳞状细胞癌 (HNSCC) 是世界上第五大最常见的恶性肿瘤，代表着 重大或国际健康问题。这些肿瘤构成了解剖学上异质性的肿瘤组 来自口腔、口咽、下咽、喉和鼻咽。虽然所有疾病都有共同的病因 与烟草和/或酒精暴露相关，源自这些不同部位的肿瘤可能表现出不同的 原发肿瘤的组织病理学无法预测但可以通过基因分析发现的行为。因此，基因 使用复杂的 eDNA 微阵列和整体蛋白质组分析对原发性肿瘤进行表达谱分析可能会 产生的信息可预测侵袭性生长、转移潜力和对几种治疗类型的反应。 拟议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能够 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， 多学科治疗在晚期 HNSCC 中的成功有限。因此可以预测肿瘤行为的新诊断 包括对治疗的反应将产生很大的临床影响。我们在拟议研究中的目标是确定具体的 预测 HNSCC 肿瘤行为和患者结果的蛋白质组变化，并开发新的、简单的 诊断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 阶段包括： 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 将计算测量的标准误差，进行的标准是具有较低置信度的可靠性 界>90%。 2-测试LC-MS分析可用于区分/分类不同类型HNSCC的可行性 临床状态。具有目标 1 的可靠性分数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，以识别单个目标或目标肽组 区分具有生存的各种临床相关性的样本，例如分期、复发和转移潜力。这 R33 阶段的具体目标将： -1- 通过 HNSCC 分析扩大全球蛋白质组学和临床数据收集 来自三个解剖部位，总共产生 135 个样本； 2- 识别和表征区分生物的肽 可变性； 3- 启动新诊断测试的开发。