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Abstract Details
Tumor-associated Autoantibodies in Combination With Alpha-Fetoprotein for Detection of Early Stage Hepatocellular Carcinoma
PLoS One. 2020 May 6;15(5):e0232247. doi: 10.1371/journal.pone.0232247. eCollection 2020.
Christopher Welberry12, Isabel Macdonald1, Jane McElveen1, Celine Parsy-Kowalska1, Jared Allen12, Graham Healey1, William Irving3, Andrea Murray1, Caroline Chapman24
Author information
1Oncimmune ltd, Nottingham, United Kingdom.
2School of Medicine, University of Nottingham, Nottingham, United Kingdom.
3NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom.
4Bowel Cancer Screening Program, Nottingham University NHS Trust, Nottingham, United Kingdom.
Abstract
Background: 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.