Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma
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 antig...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9718 |
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| author | Chang-Kyu Heo Hai-Min Hwang Won-Hee Lim Hye-Jung Lee Jong-Shin Yoo Kook-Jin Lim Eun-Wie Cho |
| author_facet | Chang-Kyu Heo Hai-Min Hwang Won-Hee Lim Hye-Jung Lee Jong-Shin Yoo Kook-Jin Lim Eun-Wie Cho |
| author_sort | Chang-Kyu Heo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T13:55:41Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:55:41Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e65683adf0ad4bcf951752d5b88bbd462023-11-21T01:41:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124971810.3390/ijms21249718Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular CarcinomaChang-Kyu Heo0Hai-Min Hwang1Won-Hee Lim2Hye-Jung Lee3Jong-Shin Yoo4Kook-Jin Lim5Eun-Wie Cho6Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, KoreaRare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, KoreaRare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, KoreaProteomeTech Inc. 401, Yangcheon-ro, Gangseo-gu, Seoul 07528, KoreaBiomedical Omics Group, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongju, Chungbuk 28119, KoreaProteomeTech Inc. 401, Yangcheon-ro, Gangseo-gu, Seoul 07528, KoreaRare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, KoreaTumor-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.https://www.mdpi.com/1422-0067/21/24/9718autoantibody biomarkerATIChepatocellular carcinomacyclic peptide mimotopehuman serum ELISA |
| spellingShingle | Chang-Kyu Heo Hai-Min Hwang Won-Hee Lim Hye-Jung Lee Jong-Shin Yoo Kook-Jin Lim Eun-Wie Cho Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma International Journal of Molecular Sciences autoantibody biomarker ATIC hepatocellular carcinoma cyclic peptide mimotope human serum ELISA |
| title | Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma |
| title_full | Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma |
| title_fullStr | Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma |
| title_full_unstemmed | Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma |
| title_short | Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma |
| title_sort | cyclic peptide mimotopes for the detection of serum anti atic autoantibody biomarker in hepato cellular carcinoma |
| topic | autoantibody biomarker ATIC hepatocellular carcinoma cyclic peptide mimotope human serum ELISA |
| url | https://www.mdpi.com/1422-0067/21/24/9718 |
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