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

Abstract

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]). Conclusion: Serum CKAP4 is a novel biomarker for HCC, and it could complement AFP in improving diagnostic accuracy.