Wang Yu, Yu Weixin, He Mingqing, Huang Yan, Wang Mingyue, Zhu Jinzhou
Department of General Surgery, Jintan Affiliated Hospital of Jiangsu University, Changzhou, China.
Department of Geriatrics, The First Affiliated Hospital of Soochow University, Suzhou, China.
Onco Targets Ther. 2018 Dec 31;12:359-364. doi: 10.2147/OTT.S189425. eCollection 2019.
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.
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.
Serum concentrations of CKAP4 were significantly elevated in the HCC group, in comparison with the three control groups (all <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, =0.001) or CKAP4 (AUC 0.821 [0.776-0.866], sensitivity 0.790, specificity 0.670, <0.001) alone to identify HCC, even though CKAP4 alone was not better than AFP (=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.
甲胎蛋白(AFP)是诊断肝细胞癌(HCC)最常用的生物标志物,但其低敏感性和特异性限制了其临床应用。细胞骨架相关蛋白4(CKAP4)是一种参与HCC发生发展的新型致癌蛋白。本研究旨在评估检测循环CKAP4是否能提高HCC的诊断准确性。
我们分析了2013年7月至2015年12月期间从两个中心招募的HCC患者、慢性乙型肝炎感染患者、肝硬化患者及健康对照者(每组100例)的数据。使用商用酶联免疫吸附测定试剂盒检测循环CKAP4水平。采用受试者工作特征曲线评估诊断准确性。
与三个对照组相比,HCC组血清CKAP4浓度显著升高(均P<0.001)。通过二元逻辑回归创建的联合生物标志物组合(AFP和CKAP4)在识别HCC方面表现优于单独的AFP(曲线下面积[AUC]0.875[0.835-0.914],敏感性0.930,特异性0.430,P=0.001)或CKAP4(AUC0.821[0.776-0.866],敏感性0.790,特异性0.670,P<0.001),尽管单独的CKAP4并不比AFP更好(P=0.093)。此外,该联合组合在识别早期HCC方面也表现更好(AUC0.922[0.833-0.961])。
血清CKAP4是HCC的一种新型生物标志物,可在提高诊断准确性方面补充AFP。