Protein Biomarker Arrays for Personalized Treatment of Prostate Cancer

描述(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，目前美国和爱尔兰的年死亡率分别超过27,000和570。目前在前列腺癌检测和分期方面的实践导致不准确的评估，经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。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。科罗拉多大学、都柏林大学医学院、爱尔兰国立大学戈尔韦分校和阿尔斯特大学。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，检测患者血清中的一小部分癌症生物标志物蛋白可以准确地检测并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小组和适当的测量设备，以确定前列腺癌的分级和分期，以及识别无癌患者。生物标记物小组将通过评估一套蛋白质集来优化，该蛋白质集结合了公认的前列腺癌生物标记物与UCD和其他研究确定的侵袭性癌症新发现的生物标记物蛋白。将利用已经在大学开发的快速、超灵敏、多功能的微流控免疫分析来开发分析和验证生物标志物小组。电脑断层扫描。同时，阿尔斯特大学将设计和制造一种简化、低成本、一次性、无标签的临床使用设备，并由整个团队进行测试。将对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进行验证。从这些机构正在进行的相关研究中获得的出色的患者随访将有助于提供更多的信息，以便在未来几年对该小组进行验证。具体目标简而言之包括：(1)利用现有的微流控阵列开发初始蛋白质组的免疫分析；(2)研究氧化还原聚合酶中介，以简化分析程序并提高灵敏度；(3)通过与有限一组血清样本的商业珠状分析相比较，验证初始蛋白质组阵列的分析准确性；(4)分析来自患者队列(爱尔兰和美国)的600份血清样本，以利用统计分析建立疾病预测和分期特征；利用这些数据来优化小组组成。(5)设计和制作一种无泵、无标记的微流控阵列，适用于临床测量一滴全血中有效的蛋白质组。这一研究策略是专门为前列腺癌诊断和个性化治疗而设计的。

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.