Characterizing Oral Cancer Progression via Saliva Proteomics

描述（由申请人提供）：口腔癌在美国每年有超过30，000例癌症病例，是全球第六大常见癌症。这些癌症的五年生存率（约50%）是癌症发展的主要部位中最差的之一，并且在过去30年中没有显著改善。可靠的分子标记物可以在早期预测这种转变，并在容易获得的临床样本中进行筛选，这将使患者能够获得更明智的治疗和监测，并有助于显着改善口腔癌患者的预后。拟议工作的总体目标是通过鉴定整个人类唾液中预测口腔癌发展的蛋白质生物标志物来解决这一关键需求。这一目标将通过三个具体目标实现：1）表征与口腔癌进展相关的分泌唾液蛋白质组的变化; 2）表征与口腔癌进展相关的脱落口腔上皮细胞蛋白质组和组织活检的变化; 3）通过靶向质谱分析筛选候选预测性口腔癌蛋白质生物标志物。将采用由组装的研究团队开发的策略，包括新颖的肽分馏方法，基于质谱的靶向生物标志物验证方法以及启用计算和生物信息学工具。将分析高度信息化的口腔癌进展模型，该模型由从口腔癌发展中期个体收集的独特临床样本组成，控制吸烟的风险因素，并能够在癌症发展的最早阶段识别诊断蛋白质变化。总之，先进技术的结合，独特的临床样本的可用性，以及集合的研究团队的集体专业知识将为成功发现和验证有前途的口腔癌临床生物标志物提供条件。 与公共卫生的关系：拟议的研究将确定临床唾液样本中预测口腔癌发展的蛋白质，提供有希望的诊断标记物，可用于常规临床患者测试。因此，拟议研究的结果将对改善临床口腔癌的诊断和治疗产生直接影响，从而减少这种癌症造成的重大痛苦和死亡。

DESCRIPTION (provided by applicant): Oral cancer accounts for over 30,000 cases of cancer per year in the United States and is the sixth most common cancer worldwide. The five-year survival rate (approximately 50%) from these carcinomas is one of the worst for the major sites of cancer development, and has not significantly improved in the past 30 years. Reliable molecular markers that can predict this transition early in the process and be screened for in readily obtained clinical samples would enable more informed treatment and monitoring of patients, and help to significantly improve the prognosis of oral cancer patients. The overall objective of the proposed work is to address this critical need by identifying protein biomarkers in whole human saliva that are predictive of oral cancer development. This objective will be achieved through three Specific Aims: 1) Characterize changes in the secreted saliva proteome associated with oral cancer progression; 2) Characterize changes in the exfoliated oral epithelial cellular proteome and tissue biopsies associated with oral cancer progression; 3) Validate candidate predictive oral cancer protein biomarkers via targeted mass spectrometric analysis. Strategies developed by the assembled research team, including novel peptide fractionation methods, targeted mass spectrometry-based biomarker validation methods, and enabling computational and bioinformatic tools will be employed. A highly informative oral cancer progression model will be analyzed, composed of unique clinical samples collected from individuals at intermediate stages of oral cancer development, controlling for the risk factor of smoking, and enabling the identification of diagnostic protein changes at the earliest stages of cancer development. Taken together, the combination of advanced technologies, availability of unique clinical samples, and the collective expertise of the assembled research team will provide for the successful discovery and validation of promising clinical biomarkers of oral cancer. RELEVANCE TO PUBLIC HEALTH: The proposed studies will identify proteins in clinical saliva samples that are predictive of oral cancer development, providing promising diagnostic markers which can be developed into routine clinical patient tests. As such the findings from the proposed studies will have a direct impact on improving the diagnosis and treatment of oral cancer in the clinic, thereby leading to a decrease in the significant suffering and death caused by this cancer.