Protein-Chip Diagnostic Assay Detection for Cancer

癌症的蛋白质芯片诊断分析检测

• 批准号: 6735490
• 负责人: Andrzej K Drukier
• 金额: $ 10.11万
• 依托单位: BIOTRACES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2004-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735490
• 关键词: angiogenesis factor; biomarker; diagnosis design /evaluation; fibroblast growth factor; human tissue; immunologic assay /test; microarray technology; neoplasm /cancer diagnosis; neoplastic growth; neoplastic transformation; photonics; proteomics; technology /technique development

DESCRIPTION (provided by applicant): Tumors produce circulating factors that have the potential to be used as diagnostic markers for the presence of the tumor. These markers may be tumor type specific, angiogenic factors, or cytokines involved in the immune response to the tumor. The diagnostic based on just one marker yield too many false positives. What is needed is the ability to assay many markers (up to 100 markers) by proteomics and then develop an accurate correlation between the presence of the markers and the presence of the tumor, thus eliminating false positives. We propose use of the supersensitive MultiPhoton Detection (MPD) enhanced to immunoassays (IA/MPD) and protein-chips (P-chips/MPD), to detect tumor markers in concentration ranges from 0.01 pg/ml level to 500 pg/ml. The technology will result in a more sensitive and specific diagnostic method, which may enable the detection of the tumors in an earlier stage of development. The objective of Phase I of this proposal is to develop the supersensitive IA/MPD assay techniques for the angiogenesis factors, Fibroblast Growth Factor-1 (FGF-1) that have been found to be expressed in many tumor types. Then clinically relevant serum samples will be screened for FGF-1, along with FGF-2, Vascular Endothelial Growth Factor (VEGF), Hepatocyte Growth Factor (HGF), IL-lbeta, IL-6, IL-10, IL-11, IL-12, and TNF-alpha, and tumor markers like Prostate Serum Antigen. Ultrasensitive IA/MPD assays currently exist for many of these factors. The clinically relevant serum samples will include pre- and post- cancer treatment patients, and healthy control subjects. Post treatment cancer patients will be monitored over time to see if marker level variations over time can predict tumor recurrence. Results will be examined to determine if a particular pattern of marker levels correlates with the presence of a tumor. The goal of Phase II is the development of the MPD enhanced P-chip. The P-chips/MPD will be adapted to a large set of markers including PSA, CEA, CA-125, and alpha-fetoprotein, cytokines and angiogenesis factors that correlate with the presence of a tumor. Additional factors, which are found expressed by tumors, but can not be detected by current relatively low sensitivity diagnostics will also be studied. Testing on clinically relevant samples will be expanded. Once the importance of concurrent measurement of several of these biomarkers are confirmed, we will develop dedicated supersensitive P-chips for quantifying up to 100 targeted marker proteins with detection ranges from 0.01 to 500 pg/ml. Thus, low cost cancer diagnostics and therapy monitoring assay will become available and a potential mechanism(s) may be suggested for earlier stage tumor formation since some of the markers may only be expressed at lower levels at the early stages.

描述(申请人提供)：肿瘤产生的循环因子有可能被用作肿瘤存在的诊断标记物。这些标记物可能是肿瘤类型特有的血管生成因子，也可能是参与肿瘤免疫反应的细胞因子。仅基于一个标志物的诊断会产生太多的假阳性。所需要的是通过蛋白质组学检测许多标记物(多达100个标记物)的能力，然后在标记物的存在和肿瘤的存在之间建立准确的关联，从而消除假阳性。我们建议使用超灵敏多光子检测(MPD)增强免疫分析(IA/MPD)和蛋白芯片(P-CHIP/MPD)来检测浓度范围从0.01pg/ml到500pg/ml的肿瘤标记物，该技术将导致一种更敏感和特异的诊断方法，从而使肿瘤的早期发现成为可能。该方案第一阶段的目标是建立超灵敏的IA/MPD检测技术，用于检测多种肿瘤中表达的血管生成因子成纤维细胞生长因子-1(FGF-1)。然后对临床相关的血清样本进行成纤维细胞生长因子-1、血管内皮生长因子(VEGF)、肝细胞生长因子(HGF)、IL-1β、IL-6、IL-10、IL-11、IL-12和肿瘤标志物(如前列腺癌血清抗原)的筛查。目前存在对其中许多因素进行超灵敏的IA/MPD分析。临床相关的血清样本将包括癌症治疗前和治疗后的患者，以及健康对照受试者。治疗后的癌症患者将随着时间的推移进行监测，看看标志物水平随时间的变化是否可以预测肿瘤复发。结果将被检查以确定标记物水平的特定模式是否与肿瘤的存在相关。第二阶段的目标是开发MPD增强型P-芯片。P-CHIPS/MPD将适应一大套标记物，包括PSA、CEA、CA-125和与肿瘤存在相关的甲胎蛋白、细胞因子和血管生成因子。还将研究由肿瘤表达的、但目前相对较低的灵敏度诊断无法检测到的其他因素。将扩大对临床相关样本的检测。一旦同时检测这些生物标记物的重要性得到确认，我们将开发专门的超灵敏P-芯片来定量多达100个靶向标记物蛋白，检测范围从0.01到500pg/ml。因此，低成本的癌症诊断和治疗监测方法将成为可能，并可能被认为是早期肿瘤形成的潜在机制(S)，因为一些标记物可能只在早期阶段较低水平表达。