Longitudinal Cancer-Specific Serum Protein Signatures

描述(由申请人提供)：血清标记物对改善癌症患者的护理和治疗具有很大的前景。尽管许多蛋白质的血清水平与各种癌症有关，但当在单个时间点单独测量时，每一种蛋白质的临床用途都有限。目前的血清标记物缺乏敏感性和特异性源于标记物蛋白基线水平的异质性以及肿瘤和患者的异质性。一种解释人和肿瘤异质性的生物标记物发现策略是使用基于纵向测量的个性化阈值来精确定义每个个体的异常水平。先前的研究表明，通过纵向测量定义的生物标记物可以比目前的标记物极大地提高特异性和敏感性。没有对这一专题进行系统的研究，这主要是因为缺乏用于这一目的的便利技术。哈布博士实验室的一项经过充分开发和验证的抗体微阵列技术现在使这种探索成为可能。抗体微阵列的多重检测能力将使我们能够测试对许多不同蛋白质使用纵向测量时的性能改进，并建立定义纵向标记使用的一般原则。此外，多路检测能力最终将允许使用组合的纵向测量来进一步提高生物标记物的性能。为了测试这一策略，我们将使用血清中许多不同的前列腺癌相关蛋白的纵向和单时间点测量来评估检测前列腺癌复发的敏感性、特异性和时间。这一新方法解决了生物标记物研究中的基本问题，并应为广泛的研究领域带来有价值的信息。前列腺癌诊断方法的成功演示将标志着它对所有类型的生物标记物研究的潜在用处。

DESCRIPTION (provided by applicant): Serum markers hold great promise for improving the care and treatment of cancer patients. Although many proteins have serum levels associated with various cancers, each has limited clinical usefulness when measured individually at single time points. The lack of sensitivity and specificity of current serum markers stems from heterogeneity in the baseline levels of the marker proteins and heterogeneity in the tumors and patients. A biomarker discovery strategy that accounts for the heterogeneity in people and tumors is to use individualized thresholds, based on longitudinal measurements, to precisely define abnormal levels for each individual. Previous research has shown that biomarkers defined by longitudinal measurements could have greatly improved specificity and sensitivity over current markers. No systematic study of this topic has been performed, largely because of the lack of a convenient technology for that purpose. A well developed and validated antibody microarray technology in the laboratory of Dr. Haab now makes this exploration possible. The multiplex detection capability of the antibody microarray will allow us to test the performance improvement upon using longitudinal measurements for many different proteins and to establish the general principles that define the use of longitudinal markers. In addition, the multiplex detection capability ultimately will allow the use of combined longitudinal measurements for even further biomarker performance improvement. To test this strategy, we will evaluate the sensitivity, specificity and time of the detection of prostate cancer recurrence using both longitudinal and single-time-point measurements of many different prostate cancer-related proteins in serum. This new approach addresses fundamental issues in biomarker research and should result in valuable information for a wide variety of research areas. The successful demonstration of the approach to prostate cancer diagnostics will signal its potential usefulness for all types of biomarker studies.