1. Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma
- Author
-
Eun-Wie Cho, Jong-Shin Yoo, Chang-Kyu Heo, Won-Hee Lim, Kook-Jin Lim, Hyejung Lee, and Hai-Min Hwang
- Subjects
Male ,Epitope ,law.invention ,lcsh:Chemistry ,Epitopes ,Mice ,autoantibody biomarker ,law ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,Mimotope ,Liver Neoplasms ,hepatocellular carcinoma ,General Medicine ,Middle Aged ,Prognosis ,Computer Science Applications ,human serum ELISA ,Hepatocellular carcinoma ,Recombinant DNA ,Biomarker (medicine) ,Female ,Liver cancer ,Adult ,Hydroxymethyl and Formyl Transferases ,Carcinoma, Hepatocellular ,Mice, Transgenic ,Peptides, Cyclic ,Article ,Catalysis ,Inorganic Chemistry ,Young Adult ,Antigen ,Multienzyme Complexes ,Peptide Library ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,cyclic peptide mimotope ,Physical and Theoretical Chemistry ,Molecular Biology ,Aged ,Autoantibodies ,business.industry ,ATIC ,Organic Chemistry ,Autoantibody ,medicine.disease ,digestive system diseases ,lcsh:Biology (General) ,lcsh:QD1-999 ,Nucleotide Deaminases ,Cancer research ,business - Abstract
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&rsquo, s efficiency can be improved by using antigenic mimicry to native antigens present in vivo.
- Published
- 2020