Open Access

Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and its usage for the diagnosis of breast cancer

  • Authors:
    • Chang-Kyu Heo
    • Hai-Min Hwang
    • Ah Ruem
    • Dae-Yeul Yu
    • Ju Yeon Lee
    • Jong Shin Yoo
    • In Gyu Kim
    • Hyang Sook Yoo
    • Sejeong Oh
    • Jeong Heon Ko
    • Eun-Wie Cho
  • View Affiliations

  • Published online on: October 26, 2012     https://doi.org/10.3892/ijo.2012.1679
  • Pages: 65-74
  • Copyright: © Heo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

A novel circulating tumor-associated autoantibody, K94, obtained from a hepatocellular carcinoma (HCC) mouse model was characterized. The target antigen of K94 autoantibody was expressed in various tumor cell lines including liver cancer, and its secretion was detectable using MCF-7 breast carcinoma cells. Proteomic analysis revealed that the protein bands reactive to K94 included cytokeratin (CK) 8 and 18, which are known to be related to tumorigenesis and form a heterotypic complex with each other. However, K94 showed no activity toward CK8 or CK18 separately. The epitope of the K94 antibody was only presented by a complex between CK8 and CK18, which was confirmed by analysis using recombinant CK8 and CK18 proteins. To formulate an assay for anti-CK8/18 complex autoantibody, a mimotope peptide reactive to K94 was selected from loop-constrained heptapeptide (-CX7C-) display phage library, of which sequence was CISPDAHSC (K94p1). A mimotope enzyme-linked immunosorbent assay (ELISA) using phage-displayed K94p1 peptide as a coating antigen was able to discriminate breast cancer (n=30) patients from normal subjects (n=30) with a sensitivity of 50% and a specificity of 82.61%. CA15.3 was detected at very low levels in the same breast cancer subjects and did not discriminate breast cancer patients from normal subjects, although it is a conventional biomarker of breast cancer. These results suggest that a mimotope ELISA composed of K94p1 peptide may be useful for the diagnosis of breast cancer.
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January 2013
Volume 42 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Heo C, Hwang H, Ruem A, Yu D, Lee JY, Yoo JS, Kim IG, Yoo HS, Oh S, Ko JH, Ko JH, et al: Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and its usage for the diagnosis of breast cancer. Int J Oncol 42: 65-74, 2013
APA
Heo, C., Hwang, H., Ruem, A., Yu, D., Lee, J.Y., Yoo, J.S. ... Cho, E. (2013). Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and its usage for the diagnosis of breast cancer. International Journal of Oncology, 42, 65-74. https://doi.org/10.3892/ijo.2012.1679
MLA
Heo, C., Hwang, H., Ruem, A., Yu, D., Lee, J. Y., Yoo, J. S., Kim, I. G., Yoo, H. S., Oh, S., Ko, J. H., Cho, E."Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and its usage for the diagnosis of breast cancer". International Journal of Oncology 42.1 (2013): 65-74.
Chicago
Heo, C., Hwang, H., Ruem, A., Yu, D., Lee, J. Y., Yoo, J. S., Kim, I. G., Yoo, H. S., Oh, S., Ko, J. H., Cho, E."Identification of a mimotope for circulating anti-cytokeratin 8/18 antibody and its usage for the diagnosis of breast cancer". International Journal of Oncology 42, no. 1 (2013): 65-74. https://doi.org/10.3892/ijo.2012.1679