Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study
Dongming Liu, Yi Luo, Lu Chen, Li-Wei Chen, Duo Zuo, Yueguo Li, Xiaofang Zhang, Jing Wu, Qing Xi, Guangtao Li, Lisha Qi, Xiaofen Yue, Xiehua Zhang, Zhuoyu Sun, Ning Zhang, Tianqiang Song, Wei Lü, Hua Guo
Abstract
Objective: Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of5 serum biomarkers (AFP, AFU, GGT-II, GPC3, and HGF) in the diagnosis of HCC. Methods: In this retrospective study, we measured the serum levels of each biomarker using ELISAs in 921 participants, including298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controlsfrom 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called “NBNC-HCC”) and patientspositive for the above indices (called “HBV-HCC and HCV-HCC”) were enrolled. The selected diagnostic model was constructedusing a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristicanalysis was used to evaluate the diagnostic accuracy. Results: The α-L-fucosidase (AFU)/α-fetoprotein (AFP) combination was best able to distinguish NBNC-HCC [area under thecurve: 0.986 (95% confidence interval: 0.958–0.997), sensitivity: 92.6%, specificity: 98.9%] from healthy controls in the test cohort.For screening populations at risk of developing HCC (CH and LC), the AFP/AFU combination improved the diagnostic specificityfor early-stage HCC [area under the curve: 0.776 (0.712–0.831), sensitivity: 52.5%, specificity: 91.6% in the test group]. In all-stageHBV-HCC and HCV-HCC, AFU was also the best candidate biomarker combined with AFP [area under the curve: 0.835 (0.784–0.877), sensitivity 69.1%, specificity: 87.4% in the test group]. All results were verified in the validation group. Conclusions: The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCCfrom at-risk patients.