Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2020; 12(10): 1167-1176
Published online Oct 15, 2020. doi: 10.4251/wjgo.v12.i10.1167
Diagnostic value of serum human epididymis protein 4 in esophageal squamous cell carcinoma
Shi-Yuan Liu, Muhammad Ahsan Bilal, Jian-Hong Zhu, Shao-Min Li
Shi-Yuan Liu, Shao-Min Li, Department of Thoracic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
Muhammad Ahsan Bilal, Department of Dermatology and Venereology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
Jian-Hong Zhu, Department of Clinical Laboratory, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
Author contributions: Liu SY and Li SM designed the research; Zhu JH, Liu SY, and Bilal MA performed the research; Liu SY and Zhu JH analyzed the data; Liu SY and Bilal MA wrote the paper.
Supported by National Natural Science Foundation of China, No. 81602023.
Institutional review board statement: The study procedures were approved by the ethical committee of the Second Affiliated Hospital of Xi'an Jiaotong University.
Informed consent statement: Patients were not required to give any informed consent to this study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment, and operative pathological examination by written consent. Individuals can’t be identified according to the data presented.
Conflict-of-interest statement: None.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Shi-Yuan Liu, MD, PhD, Associate Professor, Department of Thoracic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an 710004, Shaanxi Province, China. twinboysdoctors@163.com
Received: April 13, 2020
Peer-review started: April 13, 2020
First decision: April 26, 2020
Revised: May 24, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: October 15, 2020
Processing time: 184 Days and 3.8 Hours
Abstract
BACKGROUND

Numerous studies have demonstrated that human epididymis protein 4 (HE4) is overexpressed in various malignant tissues including ovarian, endometrial, lung, breast, pancreatic, and gastric cancers. However, no study has examined the diagnostic impact of HE4 in patient with esophageal squamous cell carcinoma (ESCC) until now.

AIM

To analyze the value of four serum tumor markers for the diagnosis of ESCC, and examine the associations of serum levels of HE4 with ESCC patients’ clinicopathological characteristics.

METHODS

The case group consisted of 80 ESCC patients, which were compared to a control group of 56 patients with benign esophageal disease. Serum levels of HE4, carcinoma embryonic antigen (CEA), alpha fetal protein, and carbohydrate antigen 19-9 (CA19-9) were detected by ELISA. The associations of serum HE4 levels with ESCC patients’ clinicopathological characteristics such as gender, tumor location, and pathological stage were also examined after operation.

RESULTS

The result of ELISA showed that serum HE4 level was significantly higher in the patients with ESCC than in the controls, and the staining intensity was inversely correlated with the pathological T and N stages. Serum HE4 levels had a sensitivity of 66.2% and specificity of 78.6% when the cutoff value was set at 3.9 ng/mL. Moreover, the combined HE4 and CA19-9 increased the sensitivity to 83.33%, and interestingly, the combination of HE4 with CEA led to the most powerful sensitivity of 87.5%. Furthermore, A positive correlation was observed between HE4 serum levels and pathological T and N stages (P = 0.0002 and 0.0017, respectively), but there was no correlation between HE4 serum levels and ESCC patient gender (P = 0.4395) or tumor location (P = 0.6777).

CONCLUSION

The results of this study suggest that detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of ESCC.

Keywords: Human epididymis protein 4; Esophageal squamous cell carcinoma; Diagnostic value; Histological stage; Clinicopathological characteristics; Clinical progression

Core Tip: Numerous studies have demonstrated that human epididymis protein 4 (HE4) is overexpressed in various malignant tissues including ovarian, endometrial, lung, breast, pancreatic, and gastric cancers. However, no study has examined the diagnostic impact of HE4 in patient with esophageal squamous cell carcinoma (ESCC) until now. In this study, we quantified serum HE4 levels via ELISA using a non-biased database consisting of 80 ESCC patients, which were compared to a control group of 56 patients with benign esophageal disease. It was found that serum HE4 was significantly higher in ESCC patients than in the control group, and the staining intensity was inversely correlated with the pathological T and N stages. It has been suggested that serum HE4 can have a potential role as an early diagnostic biomarker for ESCC.