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Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA

Tumor-associated (TA) autoantibodies are considered to be promising biomarkers for the early detection of cancer, prior to the development of clinical symptoms. In the present study, a novel TA autoantibody was detected, which may prove to be useful as a diagnostic marker of human HCC using an HBx-t...

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Autores principales: Heo, Chang-Kyu, Lim, Won-Hee, Park, Inseo, Choi, Yon-Sik, Lim, Kook-Jin, Cho, Eun-Wie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635863/
https://www.ncbi.nlm.nih.gov/pubmed/36321789
http://dx.doi.org/10.3892/ijo.2022.5448
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author Heo, Chang-Kyu
Lim, Won-Hee
Park, Inseo
Choi, Yon-Sik
Lim, Kook-Jin
Cho, Eun-Wie
author_facet Heo, Chang-Kyu
Lim, Won-Hee
Park, Inseo
Choi, Yon-Sik
Lim, Kook-Jin
Cho, Eun-Wie
author_sort Heo, Chang-Kyu
collection PubMed
description Tumor-associated (TA) autoantibodies are considered to be promising biomarkers for the early detection of cancer, prior to the development of clinical symptoms. In the present study, a novel TA autoantibody was detected, which may prove to be useful as a diagnostic marker of human HCC using an HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) mouse model. Its target antigen was identified as the bromodomain-containing protein 2 (BRD2), a transcriptional regulator that plays a pivotal role in the transcriptional control of diverse genes. BRD2 was upregulated in HCC tissues of the H-ras12V-tg mouse and human subjects, as demonstrated using western blotting or immunohistochemical analysis, with the BRD2 autoantibody. In addition, the truncated BRD2 reactive to the BRD2 autoantibody was detected in tumor cell-derived exosomes, which possibly activated TA immune responses and the generation of autoantibodies. For the detection of the serum BRD2 autoantibody, epitope mimicries of autoantigenic BRD2 were screened from a random cyclic peptide CX(7)C library with the BRD2 autoantibody. A mimotope with the sequence of CTSVFLPHC, which was cyclized by one pair of cysteine residues, exhibited high affinity to the BRD2 autoantibody and competitively inhibited the binding of the autoantibody to the cellular BRD2 antigen. The use of this cyclic peptide as a capture antigen in human serum enzyme-linked immunosorbent assay allowed the distinction of patients with HCC from healthy subjects with 64.41% sensitivity and 82.42% specificity (area under the ROC curve, 0.7761), which is superior to serum alpha-fetoprotein (AFP; 35.83% sensitivity; 100% specificity; area under the ROC curve, 0.5337) for the diagnosis of HCC. In addition, the detection of the BRD2 autoantibody combined with other autoantibody biomarkers or AFP has increased the accuracy of HCC diagnosis, suggesting that the combinational detection of cancer biomarkers, including the BRD2 autoantibody, is a promising assay for HCC diagnosis.
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spelling pubmed-96358632022-11-07 Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA Heo, Chang-Kyu Lim, Won-Hee Park, Inseo Choi, Yon-Sik Lim, Kook-Jin Cho, Eun-Wie Int J Oncol Articles Tumor-associated (TA) autoantibodies are considered to be promising biomarkers for the early detection of cancer, prior to the development of clinical symptoms. In the present study, a novel TA autoantibody was detected, which may prove to be useful as a diagnostic marker of human HCC using an HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) mouse model. Its target antigen was identified as the bromodomain-containing protein 2 (BRD2), a transcriptional regulator that plays a pivotal role in the transcriptional control of diverse genes. BRD2 was upregulated in HCC tissues of the H-ras12V-tg mouse and human subjects, as demonstrated using western blotting or immunohistochemical analysis, with the BRD2 autoantibody. In addition, the truncated BRD2 reactive to the BRD2 autoantibody was detected in tumor cell-derived exosomes, which possibly activated TA immune responses and the generation of autoantibodies. For the detection of the serum BRD2 autoantibody, epitope mimicries of autoantigenic BRD2 were screened from a random cyclic peptide CX(7)C library with the BRD2 autoantibody. A mimotope with the sequence of CTSVFLPHC, which was cyclized by one pair of cysteine residues, exhibited high affinity to the BRD2 autoantibody and competitively inhibited the binding of the autoantibody to the cellular BRD2 antigen. The use of this cyclic peptide as a capture antigen in human serum enzyme-linked immunosorbent assay allowed the distinction of patients with HCC from healthy subjects with 64.41% sensitivity and 82.42% specificity (area under the ROC curve, 0.7761), which is superior to serum alpha-fetoprotein (AFP; 35.83% sensitivity; 100% specificity; area under the ROC curve, 0.5337) for the diagnosis of HCC. In addition, the detection of the BRD2 autoantibody combined with other autoantibody biomarkers or AFP has increased the accuracy of HCC diagnosis, suggesting that the combinational detection of cancer biomarkers, including the BRD2 autoantibody, is a promising assay for HCC diagnosis. D.A. Spandidos 2022-11-01 /pmc/articles/PMC9635863/ /pubmed/36321789 http://dx.doi.org/10.3892/ijo.2022.5448 Text en Copyright: © Heo et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Heo, Chang-Kyu
Lim, Won-Hee
Park, Inseo
Choi, Yon-Sik
Lim, Kook-Jin
Cho, Eun-Wie
Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA
title Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA
title_full Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA
title_fullStr Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA
title_full_unstemmed Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA
title_short Serum BRD2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated BSA
title_sort serum brd2 autoantibody in hepatocellular carcinoma and its detection using mimotope peptide-conjugated bsa
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635863/
https://www.ncbi.nlm.nih.gov/pubmed/36321789
http://dx.doi.org/10.3892/ijo.2022.5448
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