Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer
Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer
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DOI：
10.1021/pr700804c
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
LaBaer, Joshua
中科院分区：
文献类型：
--
作者：
Anderson, Karen S.;Ramachandran, Niroshan;LaBaer, Joshua
有强有力的临床前证据表明，包括乳腺癌在内的癌症会受到免疫监视。这种通过先天性和适应性免疫系统的持续监测识别蛋白质表达、突变、折叠、糖基化和降解的变化。对肿瘤抗原的局部免疫应答在引流淋巴结中被放大，然后进入体循环。对肿瘤抗原（如p53蛋白）的抗体应答是稳健、稳定的，并且在血清中容易检测到;可能以比其同源抗原更高的浓度存在;并且是癌症的潜在高度特异性生物标志物。然而，抗体作为单一分析物具有有限的灵敏度，并且蛋白质纯化和测定特性的差异限制了其临床应用。例如，血清中的p53自身抗体对癌症患者具有高度特异性，但仅在10-20%的乳腺癌患者的血清中检测到。p53自身抗体的检测依赖于肿瘤负荷，p53突变，随着有效治疗迅速下降，但相对独立于乳腺癌亚型。尽管在乳腺癌患者的血清中已经鉴定出了数百种其他肿瘤抗原的抗体，但关于抗体免疫库对乳腺癌的特异性和临床影响知之甚少。蛋白质组学技术的最新进展具有快速识别用于乳腺癌诊断和监测的免疫应答特征的潜力。我们已经适应了可编程蛋白质微阵列在乳腺癌中的自身抗体的特异性检测。在这里，我们提出了第一个示范的应用程序的可编程蛋白质微阵列ELISA快速识别乳腺癌自身抗体。
There is strong preclinical evidence that cancer, including breast cancer, undergoes immune surveillance. This continual monitoring, by both the innate and the adaptive immune systems, recognizes changes in protein expression, mutation, folding, glycosylation, and degradation. Local immune responses to tumor antigens are amplified in draining lymph nodes, and then enter the systemic circulation. The antibody response to tumor antigens, such as p53 protein, are robust, stable, and easily detected in serum; may exist in greater concentrations than their cognate antigens; and are potential highly specific biomarkers for cancer. However, antibodies have limited sensitivities as single analytes, and differences in protein purification and assay characteristics have limited their clinical application. For example, p53 autoantibodies in the sera are highly specific for cancer patients, but are only detected in the sera of 10-20% of patients with breast cancer. Detection of p53 autoantibodies is dependent on tumor burden, p53 mutation, rapidly decreases with effective therapy, but is relatively independent of breast cancer subtype. Although antibodies to hundreds of other tumor antigens have been identified in the sera of breast cancer patients, very little is known about the specificity and clinical impact of the antibody immune repertoire to breast cancer. Recent advances in proteomic technologies have the potential for rapid identification of immune response signatures for breast cancer diagnosis and monitoring. We have adapted programmable protein microarrays for the specific detection of autoantibodies in breast cancer. Here, we present the first demonstration of the application of programmable protein microarray ELISAs for the rapid identification of breast cancer autoantibodies.