Assessment of microvessel density and tumor proximity for prognosis of cancer

评估微血管密度和肿瘤邻近性对癌症预后的影响

• 批准号: 8647495
• 负责人: Yongqiang Andrew Wang
• 金额: $ 22.5万
• 依托单位: OCEAN NANOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8647495
• 关键词: Actins; Affinity; Attention; Binding; Biological Assay; Biological Markers; Blood; Buffers; Cancer Patient; Cancer Prognosis; Caring; Cell Survival; Cells; Cellular Structures; Characteristics; Clinic; Clinical; Data; Epidermal Growth Factor Receptor; Extracellular Matrix; Fibroblasts; Formalin; Funding; Goals; Growth; Head and Neck Cancer; Head and neck structure; Image; Imaging technology; Immune; Label; Lymphatic; Lymphovascular; Malignant Neoplasms; Malignant neoplasm of lung; Manuals; Market Research; Measurable; Medical Oncologist; Methods; Modeling; Modification; Neoplasm Metastasis; Paraffin Embedding; Pathologist; Patients; Phase; Primary Neoplasm; Procedures; Prognostic Marker; Quantum Dots; Radiation Oncologist; Recurrence; Recurrent disease; Research Personnel; Risk; Sampling; Solid Neoplasm; Staining method; Stains; Surgeon; System; Technology; Technology Assessment; Testing; Tissues; Tumor Markers; Validation; antibody conjugate; base; cancer cell; cancer type; density; head and neck cancer patient; high risk; innovation; instrument; internal control; lymph nodes; macrophage; malignant stomach neoplasm; molecular imaging; neoplastic cell; operation; outcome forecast; public health relevance; technique development; technology development; tool; tumor; tumor microenvironment; tumor progression

DESCRIPTION (provided by applicant): Tumor microenvironment (TME) makes an essential contribution to tumor progression, recurrence, and metastasis. Currently, there is no standardized method to quantify major components of TME simultaneously, such as lymphovascular invasion, and to predict locoregional recurrence and metastasis of cancer. The primary goal of this project is to develop a technology for quantification of the TME signatures by using quantum dot (QD)-based immunohistofluorescence (IHF). We expect that either single or multiplexed biomarkers for the TME components can be used to assess prognosis including risk of the locoregional recurrence and metastasis. We have recently developed QD-based IHF technology for quantification of multiplexed biomarkers. Our preliminary study support us to accomplish the objective of this study, that is, to develop a molecular imaging technology for quantification of major signatures of TME as a tool for assessment of the prognosis and prediction of the recurrence and metastasis. In this project, we will focus on technique development using head and neck cancer (HNC). It is anticipated that using this technology, HNC pathologists will be able to more accurately identify patients who are at high risk for poor prognosis. This would provide valuable information to head and neck cancer surgeons, radiation oncologist, and medical oncologists to make appropriate treatment decisions. This technology also has the potential to be applied to the treatment and care of other types of cancer with appropriate modifications. The project will involve 2 Specific Aims with 5 measurable milestones. Aim 1: To prepare and validate QD- antibody (Ab) conjugates which specifically recognize blood and lymphatic vasculatures, and EGFR in formalin-fixed and paraffin embedded (FFPE) cancer tissues. Milestones for this aim are (1) completion and optimization of 4 QD-Ab conjugates with high binding affinity and selectivity; (2) establishment of the quantification method for both density of the TME signatures and their distance to tumor nests; (3) validation of the QD-based IHF by comparing this method with the conventional IHC. Aim 2: To examine whether microvessel density and tumor proximity can serve as a prognostic biomarkers and correlate them with locoregional recurrence and lymph node metastasis of HNC. Milestones for this aim are (4) completion of staining and quantification of the TME signatures using 100 FFPE samples from HNC patients with and without lymph node metastasis and recurrent disease; (5) completion of statistical analysis to correlate microvessel density and tumor proximity with clinical characteristics of HNC patients.

描述（由申请人提供）：肿瘤微环境（TME）对肿瘤进展、复发和转移做出重要贡献。目前，还没有标准化的方法来同时量化TME的主要成分，如淋巴血管浸润，并预测局部复发和转移的癌症。该项目的主要目标是开发一种通过使用基于量子点（QD）的荧光（IHF）来量化TME特征的技术。我们期望TME组分的单一或多重生物标志物可用于评估预后，包括局部复发和转移的风险。我们最近开发了基于QD的IHF技术，用于定量多重生物标志物。我们的初步研究支持我们实现本研究的目标，即开发一种分子成像技术，用于定量TME的主要特征，作为评估预后和预测复发和转移的工具。在本项目中，我们将专注于使用头颈癌（HNC）的技术开发。预计使用这项技术，HNC病理学家将能够更准确地识别预后不良的高风险患者。这将为头颈癌外科医生、放射肿瘤学家和医学肿瘤学家提供有价值的信息，以做出适当的治疗决定。这项技术也有可能被应用于其他类型的癌症的治疗和护理，并进行适当的修改。 该项目将涉及2个具体目标和5个可衡量的里程碑。目标1：制备并验证特异性识别福尔马林固定和石蜡包埋（FFPE）癌组织中的血液和淋巴管以及EGFR的QD-抗体（Ab）偶联物。实现这一目标的关键是（1）完成并优化具有高结合亲和力和选择性的4种QD-Ab缀合物;（2）建立TME特征密度及其与肿瘤巢距离的定量方法;（3）通过将该方法与常规IHC进行比较来验证基于QD的IHF。目标二：探讨微血管密度和肿瘤邻近性是否可以作为HNC的预后生物标志物，并将其与HNC的局部复发和淋巴结转移相关。该目的的关键是（4）使用来自具有和不具有淋巴结转移和复发性疾病的HNC患者的100个FFPE样品完成TME特征的染色和定量;（5）完成统计分析以将微血管密度和肿瘤接近度与HNC患者的临床特征相关联。