Repository logo
 

Tumor-associated autoantibodies in combination with alpha-fetoprotein for detection of early stage hepatocellular carcinoma.

Published version
Peer-reviewed

Change log

Authors

Welberry, Christopher 
McElveen, Jane 
Parsy-Kowalska, Celine 
Allen, Jared 

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.

Description

Keywords

Adult, Aged, Aged, 80 and over, Antigens, Neoplasm, Autoantibodies, Carcinoma, Hepatocellular, Female, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Staging, alpha-Fetoproteins

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

15

Publisher

Public Library of Science (PLoS)
Sponsorship
Medical Research Council (MR/K01532X/1)