Auto-antibody plus PSA assay for patients with prostate cancer

描述（由申请人提供）：PSA作为诊断前列腺癌的筛查方式缺乏足够的灵敏度和特异性，这强调了改善其操作特性以显著提高预测个体前列腺癌风险的质量的重要性。最近，血清来源的自体抗体（Ab）的个人前列腺癌相关抗原（PCAA）作为前列腺癌的潜在生物标志物重新受到关注。该提案的总体假设是，一种测量针对个体PCAA的循环自身抗体的多重方法补充血清PSA检测，以提高个体前列腺癌风险的预测价值。基于流式细胞术的Luminex xMAP技术具有开放式架构设计，可配置为检测多达100个独立PCAA的自体抗体。然而，单独纯化重组PCAA蛋白，然后与xMAP微球缀合在实践中是困难的。我的实验室一直专注于从临床相关的PCAA中鉴定肽表位，用于检测血清样品中存在的自体抗体。在全长蛋白质上操作肽的简单性提供了与适用于Luminex xMAP技术的微球缀合的独特机会。为了建立基于Luminex的前列腺癌多重检测，我们提出了以下具体目标：1）从我的实验室先前定义的一组临床相关PCAA中配置与B细胞表位缀合的xMAP微球集; 2）通过多重检测评估回顾性区分前列腺癌的灵敏度和特异性以及前瞻性监测肿瘤进展。来自健康供体、BPH患者、前列腺炎患者以及前列腺癌患者的每个队列中的75名受试者的血清样本将可用于拟定的研究。这项研究将提供一种新型的多重检测方法，作为前列腺癌的潜在生物标志物，用于监测疾病复发等领域。

DESCRIPTION (provided by applicant): The lack of sufficient sensitivity and specificity of PSA as a screening modality for the diagnosis of prostate cancer underscores the importance of improving its operating characteristics to considerably improve the quality of predicting individual prostate cancer risk. Recently, serum-derived autologous antibodies (Ab) to individual prostate cancer-associated antigens (PCAA) received renewed attention as potential biomarkers for prostate cancer. The overall hypothesis of the proposal is that a multiplex approach that measures circulating autoantibodies against individual PCAA complement serum PSA tests to improve the prediction value of individual prostate cancer risk. Featuring an open-architecture design, the flow-cytometry based Luminex xMAP technology can be configured to detect autologous Ab to as many as 100 independent PCAA. However, to individually purify recombinant PCAA proteins and then conjugate with xMAP microspheres is difficult in practical terms. My lab has been focusing on identification of peptide epitopes from clinically relevant PCAA for the detection of autologous Ab present in serum samples. The simplicity of manipulating peptides over full-length proteins provides a unique opportunity to conjugate with microspheres applicable for the Luminex xMAP technology. To establish the Luminex-based multiplex assay for prostate cancer, we propose the following specific aims: 1) To configurate xMAP microsphere sets conjugated with B cell epitopes from a panel of clinically relevant PCAA previously defined in my lab; 2) To assess the sensitivity and specificity for retrospectively differentiating prostate cancer as well as to prospectively monitor tumor progression by the multiplex assay. Serum sample from 75 subjects in each cohort of healthy donors, BPH patients, patients with prostatitis as well as prostate cancer patients will be available for the proposed study. This study will provide a novel multiplex assay to serve as a potential biomarker for prostate cancer in areas such as monitoring disease recurrence.