Development and Application of Mass Spectrometry Imaging to Tissue Biomarker Discovery

在这项研究计划中，我们建议开发和应用质谱学(MS)工具来发现和验证癌症生物标志物。我们将使用口腔癌样本启动该项目，因为它具有很高的临床相关性(30%的头颈部癌症发生在口腔)。我们最初的研究旨在对组织样本中不同类型的化合物进行化学定位，主要是脂质。我们将能够通过应用特定的统计工具来突出正常组织和癌组织之间的脂谱及其相对强度的差异。我们将识别最具特征性的分子，并开发多变量模型来识别患者样本中的癌症组织。在确定潜在的生物标记物后，我们将用代谢组学工具验证发现，并开发有针对性的MS技术，以增强对复杂生物组织样本中低丰度生物标记物的检测。拟议的研究将开发比目前使用的诊断技术更敏感和更准确的诊断技术。这些技术将用于癌症的早期检测和预后研究，以确定癌症复发的高可能性患者，或用于药物反应研究，以预测患者对特定治疗的反应。由于疾病的早期检测和干预对于降低医疗保健成本和改善患者预后至关重要，临床质谱学的发展将对医疗保健系统产生重大的经济影响。

In this research program, we propose to develop and apply mass spectrometric (MS) tools in the discovery and validation of cancer biomarkers. We will initiate the project using oral cavity cancer samples since it has high clinical relevance (30 percent of the head and neck region cancers occur in the oral cavity). Our initial studies are designed to chemically map different types of compounds, mostly lipids, within tissue samples. We will be able to highlight the differences in lipid profiles and their relative intensities between normal and cancer tissue by the application of specific statistics tools. We will identify the most characterising molecules and develop multivariate models to identify cancer tissues in patient samples. After identification of potential biomarkers, we will validate the findings with metabolomic tools and develop targeted MS technologies to enhance the detection of biomarkers present in low abundance in complex biological tissue samples. The proposed research will develop diagnostic technologies that are more sensitive and accurate than those currently in use. These technologies will be used in the early detection of cancers and in prognostic studies to identify patients with high potential to cancer recurrence or drug response studies to predict patient response to specific treatments. Since early disease detection and intervention are critical to reducing health care costs and improving patient outcomes, the development of clinical mass spectrometry will have significant economic impact on the healthcare system.