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Serum cytoskeleton-associated protein 4 as a biomarker for the diagnosis of hepatocellular carcinoma

Authors Wang Y, Yu W, He M, Huang Y, Wang M, Zhu J

Received 1 October 2018

Accepted for publication 8 December 2018

Published 31 December 2018 Volume 2019:12 Pages 359—364


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche

Yu Wang,1,* Weixin Yu,1,* Mingqing He,2,* Yan Huang,3 Mingyue Wang,4 Jinzhou Zhu5

1Department of General Surgery, Jintan Affiliated Hospital of Jiangsu University, Changzhou, China; 2Department of Geriatrics, The First Affiliated Hospital of Soochow University, Suzhou, China; 3Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China; 4Department of Ultrasonography, The First Affiliated Hospital of Soochow University, Suzhou, China; 5Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China

*These authors contributed equally to this work

Background: Alpha-fetoprotein (AFP) is the most commonly applied biomarker for diagnosis of hepatocellular carcinoma (HCC), but the low sensitivity and specificity limit its clinical application. Cytoskeleton-associated protein 4 (CKAP4) is a novel oncogenic protein involved in the development and progression of HCC. This study aimed to evaluate whether measurement of circulating CKAP4 could improve diagnostic accuracy for HCC.
Methods: We analyzed data for patients with HCC, chronic hepatitis B infection, and cirrhosis and healthy controls (n=100 in each group), recruited from two centers between July 2013 and December 2015. Circulating levels of CKAP4 were measured with commercial enzyme-linked immunosorbent assay kits. Receiver operating characteristics were used to evaluate diagnostic accuracy.
Results: Serum concentrations of CKAP4 were significantly elevated in the HCC group, in comparison with the three control groups (all P<0.001). The combined biomarker panel (AFP and CKAP4), created by binary logistic regression, presented better performance (area under the curve [AUC] 0.936, 95% CI [0.908–0.965], sensitivity 0.800, specificity 0.963) than AFP (AUC 0.875 [0.835–0.914], sensitivity 0.930, specificity 0.430, P=0.001) or CKAP4 (AUC 0.821 [0.776–0.866], sensitivity 0.790, specificity 0.670, P<0.001) alone to identify HCC, even though CKAP4 alone was not better than AFP (P=0.093). Furthermore, the combined panel also presented a better performance even in identifying early HCC (AUC 0.922 [0.833–0.961]).
Serum CKAP4 is a novel biomarker for HCC, and it could complement AFP in improving diagnostic accuracy.

Keywords: alpha-fetoprotein, biomarker, cytoskeleton-associated protein 4, hepatocellular carcinoma

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