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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer
Hong-Zhi Shi, Yu-Ning Wang, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen
Hong-Zhi Shi, Xiao-Hui Huang, Ke-Cheng Zhang, Hong-Qing Xi, Jian-Xin Cui, Guo-Xiao Liu, Wen-Tao Liang, Bo Wei, Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, China
Hong-Zhi Shi, Department of General Surgery, General Hospital of Armed Police Force, Beijing 100039, China
Yu-Ning Wang, Department of Surgery, Chinese PLA General Hospital, Beijing 100853, China
Wen-Tao Liang, Institute of General Surgery, Chinese PLA General Hospital, Beijing 100853, China
Author contributions: Shi HZ, Wang YN, Huang XH and Zhang KC contributed equally to this work; Shi HZ, Wang YN, Huang XH and Zhang KC designed the study; Xi HQ, Cui JX and Liu GX conducted the experiments; Liang WT, Wei B and Chen L interpreted the data; all authors approved the final version to be published.
Supported by National Natural Science Foundation of China, No. 81272698, No. 81672319 and No. 81602507.
Institutional review board statement: The study was approved by the Research Ethics Committee of the Chinese People’s Liberation Army General Hospital.
Informed consent statement: All study participants provided written consent prior to study enrollment.
Conflict-of-interest statement: All the authors have no conflict of interest.
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. Lin Chen, Department of General Surgery, Chinese PLA General Hospital, Fuxing Road 28, Beijing 100853, China. chenlinbj301@163.com
Telephone: +86-10-66938128 Fax: +86-10-68181689
Received: October 21, 2016
Peer-review started: October 25, 2016
First decision: December 28, 2016
Revised: January 3, 2017
Accepted: January 17, 2017
Article in press: January 17, 2017
Published online: March 14, 2017
AIM
To investigate the association between serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) and tissue HER2 status, and the prognostic value of serum HER2 ECD in patients with gastric cancer.
METHODS
A total of 239 patients with gastric cancer were enrolled from December 2012 to June 2013. Serum HER2 ECD was determined by chemiluminescent assay, and tissue HER2 status was evaluated by immunohistochemistry and fluorescence in situ hybridization assay. A receiver operating characteristic (ROC) curve was plotted to identify the optimal cut-off value for serum HER2 ECD assay for predicting survival in gastric cancer patients.
RESULTS
Serum HER2 ECD was significantly correlated with tissue HER2 status (P < 0.001), tumor size (P < 0.001), and intestinal type of gastric cancer (P = 0.021). Serum HER2 ECD levels differed significantly between patients with HER2-positive tissue expression and those with HER2-negative tissue expression. ROC analysis yielded an area under the curve value of 0.79 (95%CI: 0.71-0.87, P < 0.001), with a sensitivity and specificity of 0.54 (95%CI: 0.37-0.70) and 0.93 (95%CI: 0.88-0.96), respectively. With a cut-off value of 24.75 ng/mL, high serum HER2 ECD had a negative impact on overall survival of the patients (HR: 1.93, 95%CI: 1.32-4.38, P = 0.006).
CONCLUSION
Serum HER2 ECD could be a highly specific surrogate biomarker for tissue HER2 status in gastric cancer. Optimal cut-off criteria for predicting survival should be established.
Core tip: Precise determination of HER2 status is crucial for the appropriate use of HER2-targeted therapy in gastric cancer patients. Our study investigated the association between serum HER2 extracellular domain (ECD) and tissue HER2 status, and also determined the prognostic value of serum HER2 ECD in a large cohort of patients. Serum HER2 ECD could provide an easily accessible surrogate marker for tissue HER2 status, with high specificity. Furthermore, high serum HER2 ECD had a negative impact on overall survival in patients with gastric cancer.
