Predictive Markers for Oral Carcinoma Metastasis

描述（由申请人提供）：颈部转移是导致口腔鳞状细胞癌（SCC）死亡的最重要临床因素。口腔鳞状细胞癌的转移行为是高度可变的，没有临床，组织学或分子方法来确定哪些口腔鳞状细胞癌将转移。我们建议在口腔鳞状细胞癌中寻找预测转移的分子标志物。我们将采用一种全面的逐步方法，旨在汇集一小部分信息标记物，以区分有和无转移潜力的口腔SCC。目的1是利用微阵列CGH技术检测口腔鳞癌非转移性和转移性的基因组拷贝数异常。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中文献中已确定的在口腔SCC转移中发挥作用的基因。目的1和2的结果将为我们提供一种复合分子标记物（拷贝数畸变、基因表达变化和蛋白水平），可以区分有和无转移潜力的口腔SCC。然后，在目标3中，将对一组独立的口腔SCC进行分子标志物检测。总之，我们预计这些研究将建立和验证口腔鳞癌转移的预测分子标记。该项目的公共卫生相关性在于，成功鉴定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。

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.