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

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.