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Use of a Single-Chain Antibody Library for Ovarian Cancer Biomarker Discovery

机译:单链抗体库在卵巢癌生物标志物发现中的应用

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摘要

The discovery of novel early detection biomarkers of disease could offer one of the best approaches to decrease the morbidity and mortality of ovarian and other cancers. We report on the use of a single-chain variable fragment antibody library for screening ovarian serum to find novel biomarkers for the detection of cancer. We alternately panned the library with ovarian cancer and disease-free control sera to make a sublibrary of antibodies that bind proteins differentially expressed in cancer. This sublibrary was printed on antibody microarrays that were incubated with labeled serum from multiple sets of cancer patients and controls. The antibodies that performed best at discriminating disease status were selected, and their cognate antigens were identified using a functional protein microarray. Overexpression of some of these antigens was observed in cancer serum, tumor proximal fluid, and cancer tissue via dot blot and immunohistochemical staining. Thus, our use of recombinant antibody microarrays for unbiased discovery found targets for ovarian cancer detection in multiple sample sets, supporting their further study for disease diagnosis.
机译:疾病的新型早期检测生物标记物的发现可能是降低卵巢癌和其他癌症的发病率和死亡率的最佳方法之一。我们报告了使用单链可变片段抗体文库筛选卵巢血清,以发现用于检测癌症的新型生物标志物。我们用卵巢癌和无病对照血清交替淘选该文库,以制备与癌症中差异表达的蛋白质结合的抗体亚文库。该子库印在抗体微阵列上,该微阵列与来自多组癌症患者和对照的标记血清一起孵育。选择在区分疾病状态方面表现最佳的抗体,并使用功能性蛋白质微阵列鉴定其同源抗原。通过斑点印迹和免疫组织化学染色在癌症血清,肿瘤近端液体和癌症组织中观察到其中一些抗原的过度表达。因此,我们使用重组抗体微阵列进行无偏见的发现在多个样本集中发现了检测卵巢癌的靶标,从而支持了它们对疾病诊断的进一步研究。

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