Cyclic peptide mimotopes for the detection of serum anti-ATIC autoantibody biomarker in hepato-cellular carcinoma

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Cyclic peptide mimotopes for the detection of serum anti-ATIC autoantibody biomarker in hepato-cellular carcinoma
Chang Kyu Heo; Hai Min Hwang; Won-Hee Lim; H J Lee; J S Yoo; K J Lim; Eun Wie Cho
Bibliographic Citation
International Journal of Molecular Sciences, vol. 21, no. 24, pp. 9718-9718
Publication Year
Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker's efficiency can be improved by using antigenic mimicry to native antigens present in vivo.
Autoantibody biomarkerATICHepatocellular carcinomaCyclic peptide mimotopeHuman serum ELISA
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Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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