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. 项目总结/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。尽管罕见，但唾液腺有 37 种组织病理学恶性亚型和 13 种良性亚型 腺肿瘤，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 治疗时，进展期不可切除的原发性、复发性和转移性肿瘤通常是致命的。其稀有程度 肿瘤和多种组织病理学亚型给早期检测带来了重大的临床挑战， 唾液腺肿瘤患者的诊断、治疗干预和预后。 该应用程序通过推进基础研究来解决唾液腺肿瘤研究中缺失的空白 和转化科学。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以及先进的数据和生物信息学来治疗腺体肿瘤 分析开发用于唾液腺恶性肿瘤检测的基于组织的生物标志物以及潜力 使用唾液生物标志物筛查有症状的患者是否患有唾液腺恶性肿瘤/风险评估。在 额外的系统网络分析方法（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，以确定关键分子途径和基因靶标 唾液腺恶性肿瘤的发展。这些方法的共同作用将导致转化和机械化 对唾液腺肿瘤发展的见解可以进一步转化为临床应用以及 使用啮齿动物模型对唾液腺癌发生进行机制评估。 有六个具体目标来检验本应用中的假设。目标 1 是采购新鲜冷冻食品 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 腮腺肿瘤转录组的全面分析； microRNA和表观基因组使用最多 先进的 RNA 测序和甲基组学阵列。目标 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志物。这些 候选生物标志物将在目标 4 中在腮腺恶性和恶性的独立队列中进行预验证。 良性肿瘤。目标 5 是探索以下假设：恶性肿瘤中基于组织的生物标志物失调 这些患者唾液中的腮腺一致失调。最后目标 6 是一个系统网络 基于组学数据库的分析，以确定关键的生物途径和关键基因靶标 腮腺恶性肿瘤的发展。这些途径和目标结果可以在以下方面进行评估： 未来通过啮齿动物模型或细胞系进行唾液腺恶性肿瘤发展的机制研究。 我们的多学科研究团队拥有执行提议的专业知识和记录 腮腺肿瘤的分子特征以及进行机械和治疗的专业知识 转化的后续步骤，以充分实现本次 RFA 的目标。

项目成果

Discovery and prevalidation of salivary extracellular microRNA biomarkers panel for the noninvasive detection of benign and malignant parotid gland tumors.

唾液细胞外 microRNA 生物标志物组的发现和预验证，用于良性和恶性腮腺肿瘤的无创检测。

• 发表时间: 2013-06-01
• 作者: Matse, Johannes H;Yoshizawa, Janice;Wang, Xiaoyan;Elashoff, David;Bolscher, Jan G M;Veerman, Enno C I;Bloemena, Elisabeth;Wong, David T W
• 通讯作者: Wong, David T W