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dc.contributor.authorWelberry, Christopher
dc.contributor.authorMacdonald, Isabel
dc.contributor.authorMcElveen, Jane
dc.contributor.authorParsy-Kowalska, Celine
dc.contributor.authorAllen, Jared
dc.contributor.authorHealey, Graham
dc.contributor.authorIrving, William
dc.contributor.authorMurray, Andrea
dc.contributor.authorChapman, Caroline
dc.description.abstractBackground: Hepatocellular carcinoma (HCC) continues to be a leading challenge in modern oncology. Early detection via blood-based screening tests has the potential to cause a stage-shift at diagnosis and improve clinical outcomes. Tumor associated autoantibodies (TA-AAbs) have previously shown the ability to distinguish HCC from patients with high-risk liver disease. This research aimed to further show the utility of TA-AAbs as biomarkers of HCC and assess their use in combination with Alpha-fetoprotein (AFP) for detection of HCC across multiple tumor stages. Methods: Levels of circulating G class antibodies to 44 recombinant tumor associated antigens and circulating AFP were measured in the serum of patients with HCC, non-cancerous chronic liver disease (NCCLD) and healthy controls via enzyme-linked immunosorbent assay (ELISA). TA-AAb cut-offs were set at the highest Youden’s J statistic at a specificity ≥95.00%. Panels of TA-AAbs were formed using net reclassification improvement. AFP was assessed at a cut-off of 200 ng/ml. Results: Sensitivities ranged from 1.01% to 12.24% at specificities of 95.96% to 100.00% for single TA-AAbs. An ELISA test measuring a panel of 10 of these TA-AAbs achieved a combined sensitivity of 36.73% at a specificity of 89.89% when distinguishing HCC from NCCLD controls. At a cut-off of 200 ng/ml, AFP achieved a sensitivity of 31.63% at a specificity of 100.00% in the same cohort. Combination of the TA-AAb panel with AFP significantly increased the sensitivity for stage one (40.00%) and two (55.00%) HCC over the TA-AAb panel or AFP alone. Conclusions: A panel of TA-AAbs in combination with AFP could be clinically relevant as a replacement for measuring levels of AFP alone in surveillance and diagnosis strategies. The increased early stage sensitivity could lead to a stage shift with positive prognostic outcomes.
dc.publisherPublic Library of Science
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.subjectResearch Article
dc.subjectMedicine and health sciences
dc.subjectBiology and life sciences
dc.subjectResearch and analysis methods
dc.titleTumor-associated autoantibodies in combination with alpha-fetoprotein for detection of early stage hepatocellular carcinoma
prism.publicationNamePLOS ONE
datacite.contributor.supervisoreditor: Kosmoliaptsis, Vasilis
dc.contributor.orcidMacdonald, Isabel [0000-0002-0178-4463]
pubs.funder-project-idMedical Research Council (MR/K01532X/1)

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)