Molecular Characterization of Parotid Gland Tumors

腮腺肿瘤的分子特征

• 批准号: 8534892
• 负责人: David T Wong
• 金额: $ 21.14万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-07 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8534892
• 关键词: Abbreviations; Acinar Cell Carcinoma; Address; Adenocarcinoma; Adenoid Cystic Carcinoma; Adenolymphoma; Basic Science; Benign; Bioinformatics; Biological; Biological Assay; Biological Markers; Biopsy; Cell Line; Clinic; Clinical; Collection; Coupled; Critical Pathways; Data; Data Set; Databases; Detection; Development; Diagnosis; Disease; Disease Pathway; Early Diagnosis; Epigenetic Process; Evaluation; Freezing; Future; Gene Expression Profile; Gene Targeting; Generations; Genes; Genetic; Goals; Head and Neck Cancer; Head and Neck Neoplasms; Head and Neck Surgery; Head and neck structure; Heterogeneity; Human; Informatics; Interdisciplinary Study; Laboratories; Lead; Lesion; Los Angeles; Machine Learning; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of salivary gland; Messenger RNA; Methodology; MicroRNAs; Modality; Molecular; Molecular Profiling; Molecular Target; Mucoepidermoid Carcinoma; Nature; Neoplasm Metastasis; Network-based; Operative Surgical Procedures; Otolaryngology; Outcome; Parotid Cancer; Parotid Gland; Parotid Neoplasms; Pathogenesis; Pathologist; Pathology; Pathway Analysis; Pathway interactions; Patients; Primary Neoplasm; Public Health; RNA Sequences; Recurrent tumor; Research; Research Design; Resources; Risk; Risk Assessment; Rodent Model; Saliva; Salivary; Salivary Gland Neoplasms; Salivary Glands; Screening procedure; System; Technology; Testing; Therapeutic Intervention; Tissues; Translating; Translational Research; Tumor Tissue; Unresectable; Validation; Variant; Weight; abstracting; adenoma; antibody-dependent cell cytotoxicity; base; biobank; bisulfite; carcinogenesis; clinical Diagnosis; clinical application; cohort; density; epigenomics; insight; novel; oncology; outcome forecast; prognostic; transcriptomics; tumor; tumorigenesis

7. Project Summary/Abstract Salivary gland tumors constitute 1-6% of head and neck tumors numbering 3600 new cases per year in the US. Though rare, there are 37 histopathological malignant subtypes and 13 benign subtypes of salivary gland tumors, making it one of the most challenging tumors to diagnose. While surgery is the main modality of treatment, advance unresectable primary, recurrent and metastatic tumors are generally fatal. The rarity of the tumors and multiple histopathological subtypes generated major clinical challenges for the early detection, diagnosis, therapeutic interventions and prognosis of patients with salivary gland tumors. This application addresses the missing gaps in salivary gland tumor research by advancing the basic and translational sciences. Our approach is to perform comprehensive molecular characterization of salivary gland tumors using the most advanced omics technologies coupled with advanced data and bioinformatics analysis to develop tissue-based biomarkers for salivary gland malignancy detection as well as the potential use of salivary biomarkers to screen/risk assess symptomatic patients for salivary gland malignancies. In additional a systems network analysis approach (Weighted-Gene Co-Expression Network Analysis, WGCNA) will be use to examine the derived omics databases to identify pivotal molecular pathways and gene targets for salivary gland malignancy development. Collective these approaches will lead to translational and mechanistic insights for salivary tumor development that can be further translated for clinical applications as well as mechanistic evaluations using rodent models for salivary gland carcinogenesis. Six Specific Aims are in place to test the hypothesis in this application. Aim 1 is to procure fresh frozen malignant and benign parotid gland tissues from the UCLA Head & Neck Oncology Clinic. Aim 2 is to perform comprehensive profiling of parotid gland tumors' transcriptome; microRNA and epigenome using most advanced RNA sequencing and methylomics arrays. Aim 3 will perform statistical and bioinformatics analysis for the omics databases to select candidate biomarkers that can detect parotid gland malignancies. These candidate biomarkers will be pre-validated in Aim 4 in an independent cohort of parotid gland malignant and benign tumors. Aim 5 is to explore the hypothesis that tissue-based dysregulated biomarkers in malignant parotid glands are concordantly dysregulated in saliva of these patients. Finally Aim 6 is a systems network based analysis of the omics databases to identify critical biological pathways and gene targets that are pivotal in the development of parotid gland malignancies. These pathway and targets outcome can be evaluated in future mechanistic studies in salivary gland malignancy development by rodent models or cell lines. Our multidisciplinary research team has the expertise and track record to carry out the proposed molecular characterization of parotid gland tumors as well as expertise to carryout the mechanistic and translational next steps to fully materialize the goals of this RFA.

7.项目摘要/摘要 唾液腺肿瘤占头颈部肿瘤的1-6%，每年新增病例3600例。 美国。虽然罕见，但在组织病理学上有37种恶性亚型和13种良性亚型。 腺瘤，使其成为诊断最具挑战性的肿瘤之一。虽然手术是主要的治疗方式 随着治疗的进展，不能切除的原发、复发和转移肿瘤通常是致命的。世界上最罕见的 肿瘤和多种组织病理亚型给早期检测带来了重大的临床挑战， 涎腺肿瘤的诊断、治疗干预及预后。 这项应用通过推进基本的唾液腺肿瘤研究 和翻译科学。我们的方法是对唾液进行全面的分子表征 使用最先进的组学技术与先进的数据和生物信息学相结合的腺瘤 唾液腺恶性肿瘤组织生物标志物的开发及潜力分析 使用唾液生物标记物筛查/风险评估有症状的唾液腺恶性肿瘤患者。在……里面 附加系统网络分析方法(加权基因共表达网络分析，WGCNA) 将用于检查衍生的组学数据库，以确定关键的分子途径和基因靶点 唾液腺恶性发展。总的来说，这些方法将导致翻译和机械化 对唾液肿瘤发展的见解，可以进一步转化为临床应用以及 用啮齿动物模型评价唾液腺癌变的机制。 在这一应用中，有六个具体的目标来检验这一假设。目标1是采购新鲜的冷冻食品 来自加州大学洛杉矶分校头颈肿瘤诊所的恶性和良性腮腺组织。目标2是执行 腮腺肿瘤转录组的综合图谱；最常用的microRNA和表观基因组 先进的RNA测序和甲基组学阵列。AIM 3将进行统计和生物信息学分析 为组学数据库选择可以检测腮腺恶性肿瘤的候选生物标记物。这些 候选生物标记物将在AIM 4中在腮腺恶性和恶性疾病的独立队列中预先验证 良性肿瘤。目的5探讨基于组织的失调生物标志物在恶性肿瘤中的假说。 这些患者的唾液中腮腺调节失调。最后，目标6是一个系统网络 基于组学数据库的分析，以确定关键的生物学途径和基因靶点 在腮腺恶性肿瘤的发展过程中起重要作用。这些途径和目标的结果可以在 未来用啮齿动物模型或细胞系研究唾液腺恶性发展的机制。 我们的多学科研究团队拥有实施建议的专业知识和记录 腮腺肿瘤的分子特征以及开展机制和治疗的专门知识 翻译的下一步，以充分实现本RFA的目标。