摘要
在浆液的 anti-p53 抗体的存在是为癌症的 biomarker。然而，它的高敏感察觉仍然是在癌症诊断的一个问题。处理这挑战，我们使用了 fd 噬菌体，对人安全的细菌特定的病毒 nanofiber 那能被以一种无差错的方式感染主人细菌大量生产，并且遗传上设计了它显示能够在它的方面墙上认出并且捕获 anti-p53 抗体的肽。我们作为一根俘获探针采用了结果的噬菌体 nanofibers 开发连接酶的 immunosorbent 试金(ELISA ) 的一个修改版本方法，称为的 phage-ELISA。我们为 anti-p53 抗体的察觉把它比作传统的 ELISA 方法， p53-ELISA，哪个使用 recombinant 捕获 anti-p53 的野类型的 p53 蛋白质抗体。我们使用了 phage-ELISA 与恶意的肿瘤的各种各样的类型在 316 个病人的一个试验性的组检测 anti-p53 抗体。我们发现 17.7% 的察觉率(56 个积极盒子) 被 phage-ELISA 完成，它为 p53-ELISA (65 个积极盒子) 比得上 20.6% 的察觉率。然而，当噬菌体和 p53 被联合为 phage/p53-ELISA 形成捕获抗体的探针时， 30.4% 的察觉率(96 个积极盒子) 被完成。我们的工作证明由于由噬菌体 nanofibers 和 p53 的 anti-p53 抗体的联合俘获， phage/p53-ELISA 与癌症的各种各样的类型在病人为 anti-p53 抗体完成了最高诊断的精确性和察觉效率。我们的工作建议那 nanofibers 和抗原的联合，哪个俘获抗体，能导致增加的察觉敏感，它为在生命科学，临床的药，和环境科学的应用是有用的。
The presence of anti-p53 antibody in serum is a biomarker for cancer. However, its high sensitivity detection is still an issue in cancer diagnosis. To tackle this challenge, we used fd phage, a human-safe bacteria-specific virus nanofiber that can be mass-produced by infecting host bacteria in an error-free manner, and genetically engineered it to display a peptide capable of recognizing and capturing anti-p53 antibody on its side wall. We employed the resultant phage nanofibers as a capture probe to develop a modified version of the enzyme- linked immunosorbent assay （ELISA） method, termed phage-ELISA. We compared it to the traditional ELISA method for the detection of anti-p53 antibody, p53-ELISA, which uses recombinant wild-type p53 protein to capture anti-p53 antibody. We applied phage-ELISA to detect anti-p53 antibody in an experimental group of 316 patients with various types of malignant tumors. We found that a detection rate of 17.7% （56 positive cases） was achieved by phage-ELISA, which was comparable to the detection rate of 20.6% for p53-ELISA （65 positive cases）. However, when both phage and p53 were combined to form antibody-capturing probes for phage/p53-ELISA, a detection rate of 30.4% （96 positive cases） was achieved. Our work showed that owing to the combined capture of the anti-p53 antibody by both phage nanofibers and p53, the phage/p53-ELISA achieved the highest diagnostic accuracy and detection efficiency for the anti-p53 antibody in patients with various types of cancers. Our work suggests that a combination of nanofibers and antigens, both of which capture antibody, could lead to increased detection sensitivity, which is useful for applications in the life sciences, clinical medicine, and environmental sciences.
基金
Acknowledgements This study was supported by grants from the National Natural Science Foundation of China （No. 81028010）, Ministry of Science and Technology （No. 2014DFA31740） and the Department of Science and Technology of Jilin Province, China （Nos. 20130206009YY and 20130727034YY）. Y. Z., Z. G. J., P. H. Q. and C. B. M. also would like to thank the financial support from National Sdence Foundation （Nos. CMMI-1234957 and CBET-1512664）, National Institutes of Health （Nos. EB015190 and CA200504）, Department of Defense Peer Reviewed Medical Research Program （No. W81XWH- 12-1-0384）, Oklahoma Center for the Advancement of Science and Technology （No. HR14-160） and Oklahoma Center for Adult Stem Cell Research （No. 434003）.
