Multiplexed biomarker panels for early detection of prostate cancer

描述（由申请方提供）：拟定工作的目标是开发用于检测早期前列腺癌的灵敏诊断血清学检测试剂盒。目前，用于前列腺癌诊断的唯一生物标志物是测量患者血清中的前列腺特异性抗原（PSA）。PSA水平可以通过各种条件升高，并且在癌症发展时通常不处于诊断临界水平。需要替代生物标志物来更有效地诊断前列腺癌，特别是在积极治疗最有效时进行早期检测。检测对癌症相关抗原的自身免疫应答的方法正在被开发为早期癌症检测的有效手段，在与它们反应的可测量量的抗原积累用于直接抗原检测之前可检测。Chinnaiyan等人正在使用几种方法鉴定前列腺癌特异性免疫应答，包括用前列腺癌特异性cDNA表达系统以及已知的前列腺癌相关蛋白进行筛选。当组合使用时，这些抗原特异性和灵敏度检测癌症的能力上级基于PSA的测定，这是很有价值的。该提案建议将MSD敏感的Multi-Array（r）技术与Arul Chinnaiyan博士及其同事（密歇根大学）广泛的前列腺癌生物标志物专业知识和资源相结合，以开发高度特异性和敏感性的多重血清学筛查面板，用于前列腺癌的早期检测。将多种不同的感兴趣抗原（抗原表达噬菌体颗粒或纯化肽）固定在MSD Multi-Array（r）板中，其可以容纳96孔板的1-25次测定/孔。这些样本组将针对检测前列腺癌患者样本中特异性体液应答的能力进行优化，允许每孔进行多个同时测定。用于基于血清的测量的MSD多重检测板显示出低至0.1 pg/mL的灵敏度、3-5个数量级的动态范围、快速通量和最小的样品使用量（25微升/孔），这些因素对于开发用于所提议的研究的成功血清学筛查板将是至关重要的。拟议的学术/行业合作解决了NCI转化医学的目标，通过使用多功能和强大的检测平台将潜在的生物标志物从发现推向临床应用，以及评估已准备好用于癌症研究的初始临床或实验室应用的技术的IMAT目标。

DESCRIPTION (provided by applicant): The goal of the proposed work is development of sensitive diagnostic serological assay panels for detection of early stage prostate cancer. Currently, the only biomarker used in prostate cancer diagnosis is the measurement of prostate specific antigen (PSA) in patient serum. PSA levels can be elevated by various conditions, and are often not at the diagnostically critical levels when cancer develops. There is a need for alternative biomarkers to more efficiently diagnose prostate cancer, particularly for early detection when aggressive treatments would be most effective. Approaches that detect autoimmune responses to cancer-related antigens are being developed as an effective means of early cancer detection, detectible before measurable amount of the antigens they react with accumulate for direct antigen detection. Prostate cancer- specific immune responses are being identified by Chinnaiyan et al. using several approaches, including screening with prostate cancer-specific cDNA expression systems as well as known prostate cancer related proteins. Great value is seen in the ability of these antigens to specifically and sensitively detect cancer when used in combination, superior to PSA-based determinations. This proposal suggests combining MSD's sensitive Multi-Array(r) technology with the extensive prostate cancer biomarker expertise and resources of Dr. Arul Chinnaiyan and colleagues (University of Michigan), to develop highly specific and sensitive multiplex serological screening panels for early detection of prostate cancer. Multiple distinct antigens of interest (antigen-expressing phage particles, or purified peptides) will be immobilized in MSD Multi-Array(r) panels, which can accommodate 1-25 assays/well of a 96-well plate. These panels will be optimized for ability to detect specific humoral responses in prostate cancer patient samples, allowing multiple simultaneous determinations per well. MSD multiplex panels for serum-based measurements have shown sensitivities as low as 0.1 pg/mL, 3-5 orders of magnitude dynamic range, rapid throughput, and minimal sample usage ( 25 microliters/well), factors which would be critical in developing successful serological screening panels for the proposed study. The proposed academic/industry collaboration addresses NCI goals of translational medicine, by advancing potential biomarkers from discovery towards clinical applications using a versatile and robust assay platform, and the IMAT goal of evaluating technologies that are ready for initial clinical or laboratory application in cancer research.