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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.date.accessioned2020-05-07T03:04:25Z
dc.date.available2020-05-07T03:04:25Z
dc.date.issued2020-05-06
dc.date.submitted2019-08-05
dc.identifier.otherpone-d-19-22047
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/305101
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.languageen
dc.publisherPublic Library of Science
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/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
dc.typeArticle
dc.date.updated2020-05-07T03:04:25Z
prism.issueIdentifier5
prism.publicationNamePLOS ONE
prism.volume15
dc.identifier.doi10.17863/CAM.52183
dcterms.dateAccepted2020-04-10
rioxxterms.versionofrecord10.1371/journal.pone.0232247
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Kosmoliaptsis, Vasilis
dc.contributor.orcidMacdonald, Isabel [0000-0002-0178-4463]
dc.identifier.eissn1932-6203
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)