Predictive Markers for Oral Carcinoma Metastasis

口腔癌转移的预测标志物

• 批准号: 7429636
• 负责人: Brian L Schmidt
• 金额: $ 21.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-16 至 2010-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7429636
• 关键词: Behavior; Biological Markers; Candidate Disease Gene; Cessation of life; Clinical; DNA copy number; Evaluation; Excision; Formalin; Gene Expression; Genes; Genome; Genomics; Histologic; Literature; Measures; Methods; Molecular; Molecular Profiling; Morbidity - disease rate; Mouth Carcinoma; Neck; Neoplasm Metastasis; Numbers; Operative Surgical Procedures; Oral; Paraffin Embedding; Patients; Personal Satisfaction; Primary Neoplasm; Proteins; Public Health; Quality of life; RNA; Radiation therapy; Rate; Recurrence; Research Personnel; Resolution; Role; Sampling; Specimen; Squamous cell carcinoma; Techniques; Testing; base; comparative genomic hybridization; design; follow-up; improved; malignant mouth neoplasm; mouth squamous cell carcinoma; oral carcinogenesis; programs; tumor

DESCRIPTION (provided by applicant): Neck metastasis is the most significant clinical factor responsible for death from oral squamous cell carcinoma (SCC). The metastatic behavior of oral SCC is highly variable and there is not a clinical, histologic or molecular method to determine which oral SCCs will metastasize. We propose to find molecular markers in oral SCC that predict metastasis. We will pursue a comprehensive step-wise approach designed to converge on a small set of informative markers that discriminate between oral cavity SCCs with and without metastatic potential. Aim 1 is designed to use array CGH to identify genomic copy number aberrations associated with non-metastatic and metastatic oral SCCs. In Aim 2 we will analyze candidate genes in the regions of recurrent copy number aberrations identified in Aim 1. We will also evaluate the oral SCCs for genes that have been established in the literature to have a role in oral SCC metastasis. The results of Aims 1 and 2 will provide us with a composite molecular marker (copy number aberrations, gene expression changes and protein levels) that can distinguish between oral SCCs with and without metastatic potential. The molecular markers will then be tested on an independent set of oral SCCs in Aim 3. Together, we anticipate that these studies will establish and validate a predictive molecular marker for oral SCC metastasis. The Public Health relevance of this project is that successful identification of molecular markers predictive of oral cancer metastasis would profoundly decrease the morbidity associated with radiation therapy, improve tumor control rates and increase patients' quality of life.

描述(申请人提供)：颈部转移是口腔鳞状细胞癌(SCC)死亡的最重要的临床因素。口腔鳞状细胞癌的转移行为是高度多变的，目前还没有临床、组织学或分子方法来确定哪些口腔鳞癌会转移。我们建议在口腔鳞癌中寻找预测转移的分子标志物。我们将采取一种全面的循序渐进的方法，旨在集中在一小部分信息性标记物上，这些标记物区分口腔鳞状细胞癌是否有转移潜能。AIM 1旨在使用阵列CGH来识别与非转移性和转移性口腔鳞状细胞癌相关的基因组拷贝数异常。在目标2中，我们将分析在目标1中发现的重复拷贝数异常区域的候选基因。我们还将评估口腔鳞状细胞中已有文献中已建立的在口腔鳞状细胞癌转移中起作用的基因。AIMS 1和AIMS 2的结果将为我们提供一个复合的分子标记(拷贝数异常、基因表达变化和蛋白水平)来区分口腔鳞状细胞癌是否有转移潜能。这些分子标记将在AIM 3中的一组独立的口腔鳞状细胞上进行测试。我们预计，这些研究将建立并验证口腔鳞癌转移的预测分子标记。该项目的公共卫生意义在于，成功识别预测口腔癌转移的分子标志物将大大降低与放射治疗相关的发病率，改善肿瘤控制率，并提高患者的生活质量。