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（由申请人提供）：颈部转移是导致口腔鳞状细胞癌（SCC）死亡的最重要的临床因素。口腔鳞状细胞癌的转移行为变化很大，没有临床、组织学或分子方法来确定哪些口腔鳞状细胞癌会发生转移。我们建议在口腔鳞状细胞癌中寻找预测转移的分子标记。我们将寻求一种全面的逐步方法，旨在集中于一小组信息标记，以区分具有或不具有转移潜力的口腔鳞状细胞癌。目标 1 旨在使用阵列 CGH 来识别与非转移性和转移性口腔 SCC 相关的基因组拷贝数畸变。在目标 2 中，我们将分析目标 1 中确定的复发性拷贝数畸变区域中的候选基因。我们还将评估口腔 SCC 中已在文献中确定的在口腔 SCC 转移中发挥作用的基因。目标 1 和 2 的结果将为我们提供一个复合分子标记（拷贝数畸变、基因表达变化和蛋白质水平），可以区分具有和不具有转移潜力的口腔 SCC。然后，目标 3 中的分子标记将在一组独立的口腔 SCC 上进行测试。我们预计这些研究将共同​​建立并验证口腔 SCC 转移的预测分子标记。该项目与公共卫生的相关性在于，成功鉴定出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，提高肿瘤控制率并提高患者的生活质量。