Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Autor: Eun-Wie Cho, Jong-Shin Yoo, Chang-Kyu Heo, Won-Hee Lim, Kook-Jin Lim, Hyejung Lee, Hai-Min Hwang
Rok vydání: 2020
Předmět:
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
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 9718, p 9718 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 24
ISSN: 1422-0067
DOI: 10.3390/ijms21249718
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje