Molecular Determinants of Oral Tongue Cancer Metastasis

描述（由申请人提供）：肿瘤转移是癌症患者（包括口腔舌鳞状细胞癌（SCC）患者）死亡的主要原因。颈部淋巴结转移的存在是一个重要的预后因素，并在制定有关术后治疗和随访的临床决策中至关重要。然而，目前临床上对早期（T1-T2）口腔舌癌淋巴结转移的诊断并不理想。在超过30%的T1和T2舌癌患者和临床转移阴性（N 0）颈部患者中，可以预期存在隐匿性淋巴结转移。识别具有转移潜力的癌症以进行更积极的治疗是至关重要的。与转移相关的分子标记物的鉴定和基于这些标记物的预测模型的开发将改善这种可怕的癌症的管理中的临床治疗决策，并将有助于促进口腔舌SCC患者的治疗干预的发展。该提案旨在检验口腔舌癌中存在的特征基因组和表达改变的假设，这些改变将转移的肿瘤与不转移的肿瘤区分开来。患者资源到位，以允许基因组和表达研究，包括具有已知转移结果的早期（T1-T2）口腔舌癌患者（目标1）。生物信息学和生物计算专业知识已到位，以利用转移性口腔舌癌的诊断分子决定因素，并建立舌癌转移的分子分类模型（CMTCM）（目标2）。目的3是在多中心环境中测试分类模型，以评估该分类/预测模型对口腔舌癌转移的临床实用性。该提案的总体目标是将全基因组发现转化为预测模型，可以预测早期口腔舌SCC的转移潜力，从而改善口腔舌癌管理中的临床治疗决策。与公共卫生的相关性（项目叙述）：该研究项目将导致发现可用于检测口腔舌癌转移的生物标志物，这将改善口腔舌癌患者的管理和治疗。

DESCRIPTION (provided by applicant): Tumor metastasis is the dominant cause of death in cancer patients, including oral tongue squamous cell carcinoma (SCC) patients. The presence of lymph node metastasis in the neck is an important prognostic factor and crucial in making clinical decisions regarding postoperative treatments and follow ups. However, the current clinical diagnosis of lymph node metastasis for early stage (T1-T2) oral tongue cancer is not ideal. Occult nodal metastasis can be expected in over 30% of patients with T1 and T2 tongue cancers and clinically metastasis negative (N0) necks. It is critically important to identify those cancers with metastasis potential for more aggressive therapy. The identification of molecular markers associated with the metastasis and the development of a prediction model based on these markers will improve clinical treatment decisions in the management of this dreadful cancer and would help to facilitate the development of therapeutic interventions for oral tongue SCC patients. This proposal aims to test the hypothesis that signature genomic and expressional alternations exist in oral tongue cancer that distinguish tumors that metastasize from those that do not. Patient resources are in place to permit genomic and expressional studies including early stage (T1-T2) oral tongue cancer patients with known metastasis outcome (Aim 1). Bioinformatics and biocomputational expertise are in place to harness diagnostic molecular determinants in the metastatic oral tongue cancers and to build molecular classification model for tongue cancer metastasis (CMTCM) (Aim 2). Aim 3 is to test the classification models in a multi-center setting to evaluate the clinical utility of this classification/prediction models for oral tongue cancer metastasis. The overarching aim of the proposal is to translate genome-wide discoveries into a predictive model that can forecast metastatic potential of early stage oral tongue SCC, and thus improve clinical treatment decisions in the management of oral tongue cancer. Relevance to Public Health (Project Narrative): This research project will lead to the discovery of biomarkers that can be used for the detection of oral tongue cancer metastasis, which will improve the management and treatment of oral tongue cancer patients.