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

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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.

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Abbreviations

BIC:

Bayes information criterion

ELISA:

Enzyme-linked immunosorbent assay

LOOCV:

Leave one out cross validation

NHS:

Normal human ser

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Acknowledgements

We wish to acknowledge the generous donation of HCC sera from Dr. David Lee.

Funding

The authors would like to acknowledge funding received from the National Institutes of Health: 1 PO1 HL119165 (Koziol).

Author information

Authors and Affiliations

  1. Department of Molecular and Experimental Medicine, MEM290, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    James A. Koziol & Eng M. Tan

  2. Okudaira Clinic, Matsumoto, Japan

    Haruhiko Imai

  3. Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China

    Liping Dai & Jian-Ying Zhang

  4. University of Texas at El Paso, Texas, USA

    Jian-Ying Zhang

Authors
  1. James A. Koziol
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  2. Haruhiko Imai
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  3. Liping Dai
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  4. Jian-Ying Zhang
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  5. Eng M. Tan
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Contributions

Conception and design: JAK and EMT. Development of methodology: HI, LD, J-YZ, and EMT. Acquisition of data: HI, LD, J-YZ, and EMT. Analysis and interpretation of data (computational and statistical analysis): JAK, LD, and EMT. Writing and revision of the manuscript: JAK, LD, EMT. Review of the manuscript: JAK, HI, LD, J-YZ, and EMT. Study supervision: EMT.

Corresponding author

Correspondence to James A. Koziol.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval and ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. In particular, this study was approved by the Institutional Review Board of the University of Texas at El Paso and collaborating institutions. This study does not contain any studies with animals performed by any of the authors.

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Koziol, J.A., Imai, H., Dai, L. et al. Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens. Cancer Immunol Immunother 67, 835–841 (2018). https://doi.org/10.1007/s00262-018-2135-y

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  • DOI: https://doi.org/10.1007/s00262-018-2135-y

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