Protein Biomarker Arrays for Personalized Treatment of Prostate Cancer

用于前列腺癌个性化治疗的蛋白质生物标志物阵列

• 批准号: 8629949
• 负责人: James F. Rusling
• 金额: $ 35.08万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8629949
• 关键词: Affect; American Cancer Society; Applications Grants; Biological Assay; Biological Markers; Blood; Cancer Control; Cancer Detection; Cancer Diagnostics; Cancer Patient; Cessation of life; Characteristics; Clinic; Clinical; Country; Data; Detection; Developed Countries; Development; Devices; Diagnostic; Diagnostic Neoplasm Staging; Disease; Drops; Early Diagnosis; Early treatment; Electrodes; Future; Goals; Immunoassay; Institution; Ireland; Label; Lead; Longevity; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Mediation; Medical; Methods; Microfluidics; Minor; Modification; Molecular Profiling; Monitor; Oxidation-Reduction; Patients; Peroxidases; Phase; Polymers; Population; Prostate; Prostate-Specific Antigen; Proteins; Protocols documentation; Public Health; Pump; Quality of life; Research; Sampling; Serum; Set protein; Signal Transduction; Solutions; Specificity; Staging; System; Testing; Time; Translating; United States; Universities; University Hospitals; Validation; Washington; Whole Blood; anticancer research; assay development; base; cohort; college; cost; design; follow-up; improved; lifetime risk; medical schools; men; mortality; novel; public health relevance; research and development; screening; tool

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. !

概括 前列腺癌是发达国家男性最常见的恶性肿瘤 目前美国的年死亡率超过 27,000 人，爱尔兰的年死亡率为 570 人。当前的 前列腺癌检测和分期的实践通常会导致评估不准确 许多不必要的治疗会对患者的生活质量产生负面影响。 该提案包括来自大学的美国-爱尔兰研发合作伙伴赠款申请。 CT 的， 都柏林大学学院 (UCD) 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。我们的假设是检测一个小面板 患者血清中的癌症生物标志物蛋白可用于准确检测和确定阶段 和前列腺癌的分级。我们将开发一个优化的、经过验证的生物标记物组 适当的测量设备来确定前列腺癌的分级和分期以及 识别无癌症患者。将通过评估蛋白质组来优化生物标记物组 将普遍接受的前列腺癌生物标志物与新发现的生物标志物相结合 都柏林大学和其他机构的研究发现了侵袭性癌症的蛋白质。发展 生物标志物组的测定和验证将通过快速、超灵敏、多功能、 大学已经开发出微流控免疫测定法。 CT 的。同时，简化、低成本、 供临床使用的一次性、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。验证将由 UCD 学院获得的样本进行 医学和乔治华盛顿大学医院的前列腺癌患者和对照。 这些机构正在进行的相关研究的出色患者随访将促进更多 为以后几年的专家组验证提供信息。 具体目标简而言之包括： (1) 使用现有的微流控阵列开发免疫分析 用于初始蛋白质组； (2) 研究氧化还原聚合物介导以简化测定方案 并增强敏感度； (3) 验证初始蛋白质组阵列的分析准确性 与针对一组有限的血清样品的基于商业珠的测定进行比较； (4)分析>600 来自患者队列（爱尔兰和美国）的血清样本用于建立疾病预测和分期 使用统计分析的特征；使用这些数据来优化面板组成。 (5) 设计 并制造适用于临床测量的无泵、无标记微流控阵列 一滴全血中经过验证的蛋白质组。该研究策略具体是 旨在转化为临床前列腺癌诊断和个性化治疗。 ！