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Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma
Authors:Catrin H Middleton  William Irving  John F R Robertson  Andrea Murray  Celine B Parsy-Kowalska  Isabel K Macdonald  Jane McElveen  Jared Allen  Graham F Healey  Brian J Thomson  Stephen J Ryder  Stefan Holdenrieder  Caroline J Chapman
Institution:1. Centre of Excellence for Autoimmunity in Cancer, School of Medicine, University of Nottingham, Nottingham, United Kingdom.; 2. Oncimmune Ltd, Nottingham, United Kingdom.; 3. Nottingham Digestive Diseases Biomedical Research Unit, Queen''s Medical Centre, Nottingham, United Kingdom.; 4. Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.; Taipei Medicine University, Taiwan,
Abstract:

Background

Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC.

Methods

Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA.

Results

Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel.

Conclusions

This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung).
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