Protein Biomarker Arrays for Personalized Treatment of Prostate Cancer

摘要 前列腺癌是发达国家男性中最常见的恶性肿瘤， 目前美国每年的死亡率超过2.7万人，爱尔兰为570人。当前 前列腺癌检测和分期的实践导致不准确的评估，经常导致 在许多不必要的治疗中，对患者的生活质量产生了负面影响。 这项提案包括美国-爱尔兰研究与发展伙伴关系大学的赠款申请。电脑断层扫描， 都柏林大学医学院，爱尔兰国立大学戈尔韦分校，以及 阿尔斯特大学。长期目标是提供多生物标志物诊断，以实现 前列腺癌的准确分级和分期。我们的假设是，检测到一个小小组 患者血清中肿瘤生物标志物蛋白的含量可用于准确检测和确定分期 前列腺癌的分级。我们将开发一个优化的、经过验证的生物标志物面板，并 适当的测量设备以确定前列腺癌的分级和分期以及 识别没有癌症的患者。生物标记物小组将通过评估一组蛋白质来优化 前列腺癌的公认生物标记物与新发现的生物标记物的结合 UCD和其他机构的研究确定了侵袭性癌症的蛋白质。发展中的 生物标志物面板的分析和验证将使用快速、超灵敏、多功能、 微流控免疫分析已经在大学开发。电脑断层扫描。同时，简化、低成本、 临床使用的一次性、无标签设备将由阿尔斯特大学设计和制造， 并由整个团队进行测试。将对UCD学校获得的样品进行验证 来自乔治华盛顿大学医学院和乔治华盛顿大学医院的前列腺癌患者和对照组。 在这些机构对相关正在进行的研究进行出色的患者随访将有助于 为今后几年对专家组进行验证提供的信息。 简而言之，具体目标包括：(1)利用现有的微流控阵列开发免疫分析 用于最初的蛋白质面板；(2)研究氧化还原聚合物中介以简化分析程序 并提高灵敏度；(3)验证初始蛋白质板阵列的分析准确性 与基于商业珠粒的有限血清样本检测的比较；(4)分析&gt；600 来自患者队列(爱尔兰和美国)的血清样本以建立疾病预测和分期 使用统计分析的特性；使用这些数据来优化面板组成。(5)设计 并制作适合于临床测量的无泵、无标记微流控阵列 在一滴全血中验证了蛋白质面板。这一研究策略是专门的 旨在转化为前列腺癌诊断和个性化治疗的临床应用。 好了！

SUMMARY Prostate cancer is the most common malignancy among men in developed countries with current annual mortality of more than 27,000 in the United States and 570 in Ireland. Current practice in prostate cancer detection and staging leads to inaccurate assessments often resulting in many unnecessary treatments that impact negatively patient quality of life. This proposal comprises a US-Ireland R&D Partnership grant application from the Univ. of CT, University College Dublin (UCD) Medical School, National University of Ireland at Galway, and University of Ulster. The long term goal is to provide multi-biomarker diagnostics to enable accurate grading and staging of prostate cancer. Our hypothesis is that detection of a small panel of cancer biomarker proteins in patient serum can be used to accurately detect and establish stage and grade of prostate cancers. We will develop an optimized, validated biomarker panel and appropriate measurement devices to establish grade and stage of prostate cancer as well as to identify cancer-free patients. The biomarker panel will be optimized by evaluating a protein set combining general accepted biomarkers for prostate cancer with newly identified biomarker proteins for aggressive cancer identified by research from UCD and others. Development of assays and validation of the biomarker panel will be done with a rapid, ultrasensitive, versatile, microfluidic immunoassay already developed at Univ. of CT. Simultaneously, a simplified, low cost, disposable, label-free device for clinical use will be designed and fabricated by University of Ulster, and tested by the entire team. Validation will be done on samples obtained by UCD School of Medicine and George Washington University Hospital from prostate cancer patients and controls. Excellent patient follow-up from related ongoing studies in these institutions will facilitate additional information for validation of the panel in later years. Specific aims in brief include: (1) Develop immunoassays using an existing microfluidic array for an initial panel of proteins; (2) Investigate redox polymer mediation to simplify assay protocols and enhance sensitivity; (3) Validate analytical accuracy of array for initial protein panel by comparing to commercial bead based assays for a limited set of serum samples; (4) Analyze >600 serum samples from patient cohorts (Irish and USA) to establish disease prediction and staging characteristics using statistical analyses; use these data to optimize panel composition. (5) Design and fabricate a pump-free, label-free microfluidic array suitable for clinical measurements of the validated protein panel in a single drop of whole blood. This research strategy is specifically designed to translate to the clinic for prostate cancer diagnostics and personalized therapy. !