Biomarker Detection Using NAPPA Tumor Antigen Arrays

使用 NAPPA 肿瘤抗原阵列检测生物标志物

• 批准号: 8882672
• 负责人: Karen Sue Anderson
• 金额: $ 19.24万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-11 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8882672
• 关键词: Age; Algorithms; Antibodies; Antibody Specificity; Antigens; Autoantibodies; Biological Assay; Biological Markers; Blinded; Breast; Breast Cancer Early Detection; Cancer Patient; Cell Cycle; Characteristics; Clinical Research; Collection; Complement; Complementary DNA; Detection; Development; Disease; ERBB2 gene; Early Detection Research Network; Ensure; Enzyme-Linked Immunosorbent Assay; Female; Frequencies; Funding; Genes; Goals; Guidelines; Hormone Receptor; In Vitro; Individual; Laboratories; Malignant Neoplasms; Methods; Microarray Analysis; Morbidity - disease rate; Mutation; Normal Range; Ovarian; Patients; Pattern; Performance; Phase; Predictive Value; Printing; Process; Protein Microchips; Protocols documentation; Research Personnel; Screening for cancer; Sensitivity and Specificity; Serum; Specificity; Staging; Testing; Translating; Tumor Antigens; Validation; Variant; Western Blotting; breast density; clinical Diagnosis; density; malignant breast neoplasm; mortality; novel; overexpression; phase 2 study; protein expression; research study; screening; sex; tool; triple-negative invasive breast carcinoma; tumor; validation studies

DESCRIPTION (provided by applicant): The overall goal of this project is to identify autoantibody biomarkers in sera that can be readily used for the early detection of cancer. Antibodies are induced by tumor-specific alterations in protein expression, mutation, degradation, or localization, with high specificity. We have developed a novel programmable protein microarray technology (NAPPA), which uses printed cDNA encoding tumor antigens that are translated in vitro. We have been funded for the past four years as an EDRN Biomarker Development Laboratory to develop NAPPA as a clinical research tool and to employ it for the detection of autoantibody biomarkers for breast cancer, and have screened over 700 sera and identified 32 novel breast and 23 ovarian biomarkers that have undergone blinded validation studies. Here, we propose to increase the feature density of NAPPA arrays in order to accommodate the increasing size of our cDNA collection, which now approaches 10,000 unique genes (Aim 1) and to develop a method for producing glycoproteome arrays (Aim 2). Both of these methods will enhance autoantibody biomarker discovery by increasing the number and quality of the antigens screened. Aim 3 will use the results of Aims 1 and 2 to expand the top breast cancer biomarkers that have been identified to focus on particular subtypes of breast cancer that are more difficult to detect including Her2+ breast cancers, triple-negative (ER-PR-Her2-) breast cancers, and cancers that occur in the setting of high breast density. Association of antibody detection and tumor antigen expression will be explored. Aim 4 will assess the performance characteristics of the combined set of top breast cancer biomarkers in Phase II studies using sera collected in multicenter clinical studies. Aim 5 will focus on the utility of these biomarkers to detect disease prior to clinical diagnosis. At the end of these experiments, our goal is to identify autoantibody serum signatures that can be used by EDRN CEVCs in further Phase III independent validation studies for the early detection of breast cancer according to the EDRN biomarker discovery guideline.

描述(由申请人提供)：本项目的总体目标是在血清中识别可用于癌症早期检测的自身抗体生物标记物。抗体是由肿瘤特异性蛋白表达、突变、降解或定位的改变引起的，具有高度的特异性。我们开发了一种新的可编程蛋白质微阵列技术(NAPPA)，它使用打印的编码肿瘤抗原的cDNA，并在体外翻译。在过去的四年里，我们作为EDRN生物标记物开发实验室得到了资助，以开发NAPPA作为临床研究工具，并将其用于检测乳腺癌的自身抗体生物标记物，并筛选了700多份血清，确定了32种新的乳腺癌和23种卵巢生物标记物，进行了盲法验证研究。在这里，我们建议增加NAPPA阵列的特征密度，以适应我们不断增长的cDNA集合的大小，目前我们的集合已接近10,000个独特基因(目标1)，并开发了一种生产糖蛋白质组阵列的方法(目标2)。这两种方法都将通过增加筛选的抗原的数量和质量来促进自身抗体生物标记物的发现。AIM 3将利用AIMS 1和2的结果来扩展已确定的顶级乳腺癌生物标记物，以专注于更难检测的特定乳腺癌亚型，包括Her2+乳腺癌、三阴性(ER-PR-Her2-)乳腺癌以及发生在高乳腺密度环境中的癌症。将探讨抗体检测和肿瘤抗原表达之间的关系。目的4将使用在多中心临床研究中收集的血清，在第二阶段研究中评估顶级乳腺癌生物标记物组合的性能特征。目标5将重点放在这些生物标志物在临床诊断之前检测疾病的用途上。在这些实验结束时，我们的目标是根据EDRN生物标记物发现指南，确定EDRN CEVCs可以在进一步的第三阶段独立验证研究中用于乳腺癌早期检测的自身抗体血清签名。