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Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma

Authors Chen H, Zhang Y, Li S, Li N, Chen Y, Zhang B, Qu C, Ding H, Huang J, Dai M

Received 1 March 2018

Accepted for publication 17 April 2018

Published 10 July 2018 Volume 2018:10 Pages 1947—1958

DOI https://doi.org/10.2147/CMAR.S167036

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Hongda Chen,1,* Yue Zhang,1,2,* Siwen Li,3,* Ni Li,1 Yuhan Chen,4 Bei Zhang,3 Chunfeng Qu,1 Huiguo Ding,4 Jian Huang,3,5 Min Dai1

1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Office of Scientific Research, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China; 3Liver Research Center, Experimental Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China; 4Department of Gastrointestinal and Hepatology, Beijing You’ An Hospital Affiliated to Capital Medical University, Beijing, China; 5National Clinical Research Center of Digestive Diseases, Beijing, China

*These authors contributed equally to this work

Background: Although a number of serum biomarkers for detection of hepatocellular carcinoma (HCC) have been explored, their exact diagnostic value remains unclear. We aimed to conduct a direct comparison of five representative serum biomarkers for detecting HCC and to derive multi-marker prediction algorithms.
Patients and methods: In total, 846 patients were recruited from three hospitals in China, including 202 HCC patients, 226 liver cirrhosis patients, 215 chronic hepatitis B virus-infected patients, and 203 healthy volunteers. Serum levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), des-gamma-carboxyprothrombin (DCP), squamous cell carcinoma antigen, and centromere protein F autoantibody were measured by ELISA. The diagnostic performances of individual biomarkers and multi-marker combinations were evaluated by receiver operating characteristics analysis. The bootstrapping method was adopted to adjust for potential overfitting of all diagnostic indicators.
Results: DCP exhibited the best diagnostic performance, with areas under the curve (AUC) for detecting HCC of 0.82 (95% CI 0.64–0.80) and sensitivity of 65.2% (95% CI 63.3–82.1%) at 90% specificity. Of note, DCP showed similar diagnostic efficacy for detecting AFP-positive and AFP-negative HCC. After a comprehensive search for multi-marker combinations, a two-marker prediction algorithm including AFP and DCP was constructed and yielded an AUC of 0.87 (95% CI 0.68–0.84) for detecting HCC. In addition, the combination showed good ability in discriminating early-stage HCC and decompensated liver cirrhosis, with an AUC of 0.81 (95% CI 0.75–0.86).
Conclusion: DCP could be a complementary biomarker in the early diagnosis of HCC. The constructed multi-marker prediction algorithms could contribute toward distinguishing HCC from non-malignant chronic liver diseases.

Keywords: early detection, liver cirrhosis, prediction model

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