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Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

ABSTRACT: BACKGROUND:Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests? METHODS:We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis. RESULTS:The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year. CONCLUSIONS:We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

SUBMITTER: Koziol JA

PROVIDER: S-EPMC5930126 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

Koziol James A JA Imai Haruhiko H Dai Liping L Zhang Jian-Ying JY Tan Eng M EM

Cancer immunology, immunotherapy : CII 20180301 5

<h4>Background</h4>Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests?< ...[more]

PMID: 29497780

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Project 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 CX7C 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.

Dataset Information

Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

Publications

Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

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