Molecular Determinants of Oral Tongue Cancer Metastasis

描述(申请人提供)：肿瘤转移是癌症患者的主要死亡原因，包括口腔舌鳞状细胞癌(SCC)患者。颈部淋巴结转移的存在是一个重要的预后因素，对术后治疗和随访的临床决策至关重要。然而，目前临床对早期(T1-T2)口腔舌癌淋巴结转移的诊断并不理想。在T1和T2舌癌和临床转移阴性(N0)颈部的患者中，超过30%的患者可以预见到隐匿性淋巴结转移。识别那些具有转移潜力的癌症以进行更积极的治疗是至关重要的。识别与转移相关的分子标志物，并基于这些标志物建立预测模型，将改善这种可怕的癌症的临床治疗决策，并有助于发展口腔鳞状细胞癌患者的治疗干预措施。这项提议旨在检验一种假设，即口腔舌癌存在标志性的基因组和表达变化，以区分转移的肿瘤和没有转移的肿瘤。患者资源已经到位，可以进行包括早期(T1-T2)口腔舌癌患者在内的基因组和表达研究(目标1)。生物信息学和生物计算技术已经到位，以利用口腔转移癌的诊断分子决定因素，并建立舌癌转移(CMTCM)的分子分类模型(目标2)。目的3是在多中心环境下检验分类模型，以评价该分类/预测模型在口腔舌癌转移中的临床应用价值。该提案的总体目标是将全基因组范围的发现转化为预测模型，该模型可以预测早期口腔舌癌的转移潜力，从而改善口腔舌癌的临床治疗决策。与公共卫生相关(项目叙述)：这项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.