Oncotarget

Research Papers:

The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study

Vandana M. Sagar, Kathyrn Herring, Stuart Curbishley, James Hodson, Peter Fletcher, Salil Karkhanis, Homoyon Mehrzad, Pankaj Punia, Tahir Shah, Shishir Shetty and Yuk Ting Ma _

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Oncotarget. 2021; 12:2338-2350. https://doi.org/10.18632/oncotarget.28136

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Abstract

Vandana M. Sagar1,*, Kathyrn Herring2,*, Stuart Curbishley1, James Hodson3, Peter Fletcher4, Salil Karkhanis5, Homoyon Mehrzad5, Pankaj Punia2, Tahir Shah6, Shishir Shetty1,6,# and Yuk Ting Ma1,2,#

1 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

2 The Cancer Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

3 Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

4 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK

5 Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

6 The Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

* These authors contributed equally to this work (joint first authors)

# These authors contributed equally to this work (joint senior authors)

Correspondence to:

Yuk Ting Ma, email: [email protected]

Keywords: hepatocellular carcinoma; biomarker; PIVKA-II

Received: May 31, 2021     Accepted: November 10, 2021     Published: November 23, 2021

Copyright: © 2021 Sagar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Prothrombin induced by vitamin K absence II (PIVKA-II) has recently been validated internationally as a diagnostic biomarker for hepatocellular carcinoma (HCC), as part of the GALAD model. However, its role as a treatment response biomarker has been less well explored. We, therefore, undertook a prospective study at a tertiary centre in the UK to evaluate the role of PIVKA-II as a treatment response biomarker in patients with early, intermediate and advanced stage HCC. In a cohort of 141 patients, we found that PIVKA-II levels tracked concordantly with treatment response in the majority of patients, across a range of different treatment modalities. We also found that rises in PIVKA-II levels almost always predated radiological progression. Among AFP non-secretors, PIVKA-II was found to be informative in 60% of cases. In a small cohort of patients undergoing liver transplantation, pre-transplant PIVKA-II levels predicted for microvascular invasion and poorer differentiation. Our results demonstrate the potential utility of PIVKA-II as a treatment response biomarker and in predicting microvascular invasion, in a Western population. PIVKA-II demonstrated improved performance over AFP but, as a single biomarker, its performance was still limited. Further larger prospective studies are recommended to evaluate PIVKA-II as a treatment response biomarker, within the GALAD model.


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