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Original Article | Open Access

Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study

Dongming Liu1,*, Yi Luo2,*, Lu Chen1,*, Liwei Chen2, Duo Zuo3, Yueguo Li3, Xiaofang Zhang4, Jing Wu5, Qing Xi2, Guangtao Li2, Lisha Qi6, Xiaofen Yue7, Xiehua Zhang8, Zhuoyu Sun9, Ning Zhang10, Tianqiang Song1( ), Wei Lu1 ( ), Hua Guo2( )
Department of Hepatobiliary, Liver Cancer Research Center for Prevention and Therapy
Department of Tumor Cell Biology
Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Medical Laboratory, Tianjin Medical University General Hospital, Tianjin 300052, China
Clinical Laboratory, Tianjin Third Central Hospital, Tianjin 300170, China
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
Department of Tianjin Research Institute of Liver Diseases, Tianjin Second People’s Hospital, Tianjin 300192, China
Department of Infectious Diseases, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, China
Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China
The Center for Translational Cancer Research, Peking University First Hospital, Beijing 100034, China

*These authors contributed equally to this work.

Show Author Information

Abstract

Objective

Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of 5 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, including 298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controls from 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called “NBNC-HCC”) and patients positive for the above indices (called “HBV-HCC and HCV-HCC”) were enrolled. The selected diagnostic model was constructed using a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristic analysis 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 the curve: 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 specificity for 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-stage HBV-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 HCC from at-risk patients.

Keywords

biomarkerserumHepatocellular carcinomaAFPAFU

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 18 Issue 1,
February 2021
Pages 256-270
DOI: 10.20892/j.issn.2095-3941.2020.0207
Cite this article:
Liu D, Luo Y, Chen L, et al. Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study. Cancer Biology & Medicine, 2021, 18(1): 256-270. https://doi.org/10.20892/j.issn.2095-3941.2020.0207

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Received: 04 May 2020
Accepted: 13 October 2020
Published: 01 February 2021
©2021 Cancer Biology & Medicine.

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