Liu Brian C-S, Dijohnson Daniel A, O'Rourke Dennis J
Brigham and Women's Hospital, Harvard Medical School, Division of Urology, Molecular Urology Laboratory , 221 Longwood Ave., LMRC-610, Boston, MA 02115 , USA +1 617 732 4973 ; +1 617 582 6191 ;
Expert Opin Med Diagn. 2012 May;6(3):187-96. doi: 10.1517/17530059.2012.672969. Epub 2012 Mar 22.
Proteins not present in normal cells, that is, cancer cells, may elicit a host immune response that leads to the generation of antibodies that might react with these tumor-associated proteins. In recent years, a growing number of reports have showed that autoantibody profiling may provide an alternative approach for the detection of cancer. However, most studies of antigen-autoantibody reactivity have relied on recombinant proteins. Recombinant proteins lack the proper post-translational modifications present in native proteins. Because of this limitation, native or natural protein antigen microarrays are gaining popularity for profiling antibody responses.
i) To illustrate some examples of autoantibodies as signatures for early stage cancer; ii) to briefly outline the various protein antigen microarray platforms; iii) to illustrate the use of native or natural protein microarrays in the discovery of potential biomarkers and iv) to discuss the advantages of native protein antigen microarrays over other approaches.
The nature of protein microarray platforms is conducive to multiplexing, which amplifies the potential for uncovering effective biomarkers for many significant diseases. However, the major challenge will be in integrating microarray platforms into multiplexed clinical diagnostic tools, as the main drawback is the reproducibility and coefficient of variation of the results from array to array, and the transportability of the array platform to a more automatable platform.
正常细胞即癌细胞中不存在的蛋白质,可能引发宿主免疫反应,导致产生可能与这些肿瘤相关蛋白质发生反应的抗体。近年来,越来越多的报告表明,自身抗体谱分析可能为癌症检测提供一种替代方法。然而,大多数抗原 - 自身抗体反应性研究依赖于重组蛋白。重组蛋白缺乏天然蛋白中存在的适当翻译后修饰。由于这一局限性,天然或天然蛋白抗原微阵列在分析抗体反应方面越来越受欢迎。
i)举例说明自身抗体作为早期癌症标志物的一些例子;ii)简要概述各种蛋白质抗原微阵列平台;iii)说明天然或天然蛋白质微阵列在发现潜在生物标志物中的应用;iv)讨论天然蛋白质抗原微阵列相对于其他方法的优势。
蛋白质微阵列平台的性质有利于多重检测,这增加了为许多重大疾病发现有效生物标志物的潜力。然而,主要挑战将是将微阵列平台整合到多重临床诊断工具中,因为主要缺点是阵列之间结果的重现性和变异系数,以及阵列平台向更自动化平台的可运输性。