Protein Biomarker Arrays for Personalized Treatment of Prostate Cancer

描述（由申请人提供）：前列腺癌是发达国家男性中最常见的恶性肿瘤，目前美国的年死亡率超过27，000人，爱尔兰为570人。目前前列腺癌检测和分期的实践导致不准确的评估，通常导致许多不必要的治疗，对患者的生活质量产生负面影响。 该提案包括来自CT大学，都柏林大学学院（UCD）医学院，高威的爱尔兰国立大学和阿尔斯特大学的美国-爱尔兰研发合作伙伴关系资助申请。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，检测患者血清中的一小组癌症生物标志物蛋白可用于准确检测和确定前列腺癌的分期和分级。我们将开发一个优化的，经过验证的生物标志物面板和适当的测量设备，以确定前列腺癌的等级和阶段，以及确定无癌患者。生物标志物面板将通过评估蛋白质集进行优化，该蛋白质集将普遍接受的前列腺癌生物标志物与UCD和其他研究确定的侵袭性癌症的新确定的生物标志物蛋白质相结合。检测方法的开发和生物标志物面板的验证将使用CT大学已经开发的快速，超灵敏，多功能，微流体免疫测定来完成。同时，阿尔斯特大学将设计和制造一种简化的、低成本的、一次性的、无标签的临床使用装置，并由整个团队进行测试。验证将在UCD医学院和乔治华盛顿大学医院从前列腺癌患者和对照组获得的样本上进行。这些机构正在进行的相关研究的优秀患者随访将有助于在以后的几年中验证面板的额外信息。 具体目标简要地包括：（1）使用现有的微流体阵列开发用于初始蛋白质组的免疫测定;（2）研究氧化还原聚合物介导以简化测定方案并提高灵敏度;（3）通过与用于有限的血清样品组的基于商业珠的测定进行比较，验证用于初始蛋白质组的阵列的分析准确性;（4）分析来自患者组群（爱尔兰和美国）的>600个血清样品，以使用统计分析建立疾病预测和分期特征;使用这些数据优化组组成。(5)设计和制造无泵、无标记的微流控阵列，适用于临床测量单滴全血中的经验证蛋白质组。这项研究策略是专门设计的，以转化为前列腺增生症的诊断和个性化治疗的临床。

DESCRIPTION (provided by applicant): 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 informationfor 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 polyme 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 cancr diagnostics and personalized therapy.