Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma
Ting Wang, Mei Liu, Su-Jun Zheng, Dan-Dan Bian, Jin-Yan Zhang, Jia Yao, Qing-Fen Zheng, A-Meng Shi, Wen-Han Li, Lu Li, Yu Chen, Jin-Hai Wang, Zhong-Ping Duan, Lei Dong
Ting Wang, A-Meng Shi, Lu Li, Jin-Hai Wang, Lei Dong, Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Ting Wang, Mei Liu, Su-Jun Zheng, Dan-Dan Bian, Jin-Yan Zhang, Jia Yao, Qing-Fen Zheng, Yu Chen, Zhong-Ping Duan, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
Wen-Han Li, Department of Surgical Oncology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710043, Shaanxi Province, China
Author contributions: Wang T and Liu M contributed equally to this work; Wang T and Liu M designed the research and wrote the manuscript; Wang T, Zheng SJ, Bian DD, Zhang JY and Chen Y collected the serum samples; Wang T, Yao J, Zheng QF, Shi AM and Li WH recorded the data; Wang T performed the research; Wang T, Li L and Wang JH analyzed the data; Duan ZP and Dong L designed the research and modified the manuscript; and all authors have read and approved the final version to be published.
Supported by Clinical Research Cooperation Fund of the Capital Medical University, No. 15JL67; Project of Science and Technology Development Plan of Beijing Municipal Education Commission, No. KM201610025021; High-Tech Personnel Training Program of Beijing Health System, No. 2015-3-104; Beijing Municipal Science and Technology Commission, No. Z151100004015066; and Shaanxi Science and Technology Coordination and Innovation Project, No. 2016KTZDSF02-02.
Institutional review board statement: This study was approved by the Ethics Committee of Beijing You’an Hospital, Capital Medical University, Beijing, China.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors declared that there is no conflict of interest related to this study.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Lei Dong, Professor, Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China.
donglei6655@126.com
Telephone: +86-29-87679272 Fax: +86-29-87678758
Received: January 10, 2017
Peer-review started: January 11, 2017
First decision: February 9, 2017
Revised: February 21, 2017
Accepted: March 31, 2017
Article in press: March 31, 2017
Published online: May 21, 2017
Processing time: 129 Days and 18 Hours
AIM
To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC).
METHODS
Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues.
RESULTS
The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls (P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%.
CONCLUSION
Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.
Core tip: We firstly and specifically investigated the diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). We retrospectively evaluated the prevalence and diagnostic value of autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins and their different combinations in 56 AFP-negative HCC patients by enzyme-linked immunosorbent assay and western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC. Our study demonstrated that autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.
