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: 8796182
• 负责人: James F. Rusling
• 金额: $ 33.31万
• 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/8796182
• 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; Health; 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; 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; personalized medicine; research and development; screening; temporal measurement; tool

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.

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，目前美国每年有超过27,000人死亡，爱尔兰有570人死亡。目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、都柏林大学医学院、爱尔兰国立大学戈尔韦分校和阿尔斯特大学的美国-爱尔兰研发伙伴关系拨款申请。长期目标是提供多种生物标志物诊断，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、有效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分期，并确定无癌患者。生物标志物面板将通过评估一组蛋白质来优化，该蛋白质集结合了一般接受的前列腺癌生物标志物和UCD和其他研究发现的新发现的侵袭性癌症生物标志物蛋白质。生物标志物面板的检测和验证将通过CT大学已经开发的快速、超灵敏、通用的微流体免疫分析来完成。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中获得的样本进行验证。这些机构中正在进行的相关研究的优秀患者随访将为今后验证该小组提供更多信息。简要地说，具体目标包括：(1)使用现有的微流控阵列对初始蛋白质面板进行免疫分析；(2)研究氧化还原聚合介质，简化检测方案，提高灵敏度；(3)通过对有限的血清样本进行比较，验证初始蛋白面板阵列的分析准确性；(4)分析来自爱尔兰和美国患者队列的bbb600份血清样本，利用统计学分析建立疾病预测和分期特征；使用这些数据来优化面板组成。(5)设计和制造一种无泵、无标签的微流控阵列，适用于临床测量一滴血中经过验证的蛋白质面板。这项研究策略是专门设计用于前列腺癌诊断和个性化治疗的临床。