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Serum autoantibody measurement for the detection of hepatocellular carcinoma

Middleton, Catrin H.; Irving, William; Robertson, John F.R.; Murray, Andrea; Parsy-Kowalska, Celine B.; Macdonald, Isabel K.; McElveen, Jane; Allen, Jared; Healey, Graham F.; Ryder, Stephen J.; Holdenrieder, Stefan; Chapman, Caroline J.; Thomson, Brian J.

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Authors

Catrin H. Middleton

William Irving

Andrea Murray

Celine B. Parsy-Kowalska

Isabel K. Macdonald

Jane McElveen

Jared Allen

Graham F. Healey

Stephen J. Ryder

Stefan Holdenrieder

Caroline J. Chapman

Brian J. Thomson



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).

Journal Article Type Article
Acceptance Date Jul 2, 2014
Online Publication Date Aug 5, 2014
Publication Date Aug 5, 2014
Deposit Date Sep 5, 2017
Publicly Available Date Apr 12, 2019
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 8
Article Number e103867
Pages 1-9
DOI https://doi.org/10.1371/journal.pone.0103867
Public URL https://nottingham-repository.worktribe.com/output/1118375
Publisher URL https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103867
PMID 25093332

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