Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2015; 21(20): 6271-6279
Published online May 28, 2015. doi: 10.3748/wjg.v21.i20.6271
Relationship between expression of NADPH oxidase 2 and invasion and prognosis of human gastric cancer
Peng Wang, Qiao Shi, Wen-Hong Deng, Jia Yu, Teng Zuo, Fang-Chao Mei, Wei-Xing Wang
Peng Wang, Qiao Shi, Jia Yu, Teng Zuo, Fang-Chao Mei, Wei-Xing Wang, Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Wen-Hong Deng, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Wang P participated in the design of the study, performed the majority of experiments and wrote this article; Shi Q participated in the design of this study, performed the Western blot and helped to write the paper; Wang P and Shi Q contributed equally to this work and should be considered co-first authors; Deng WH participated in the design of the study and collected the clinical samples; Yu J participated in the design of the study, collected the clinical samples and did the work of follow-up visit; Zuo T and Mei FC participated in the design of the study and did the work of follow-up visit; Wang WX participated in the design of this study and collected all the human material in addition to providing financial support for this work.
Supported by National Natural Science Foundation of China, No. 81370562.
Ethics approval: This study was reviewed and approved by the Committee for Ethical Review of Research involving Human Subjects of Remin Hospital of Wuhan University, Wuhan, China and carried out according to the Declaration of Helsinki.
Informed consent: All study participants, or their legal guardian provided informed written consent prior to study enrollment.
Conflict-of-interest: No potential conflicts of interest relevant to this article are reported.
Data sharing: 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: Wei-Xing Wang, MD, Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China. sate.llite@163.com
Telephone: +86-27-88041911 Fax: +86-27-88042292
Received: November 25, 2014
Peer-review started: November 26, 2014
First decision: January 22, 2015
Revised: February 10, 2015
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: May 28, 2015
Abstract

AIM: To assess the expression and prognostic value of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) in gastric cancer, and its correlation with vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR).

METHODS: Tumor and adjacent tissues were obtained from 123 patients who underwent radical surgery for gastric cancer at Renmin Hospital of Wuhan University from 2008-2009. The expression of NOX2, VEGF, EGFR and CD68 in tumor tissues was detected by immunohistochemistry. The expression of NOX2 in gastric cancer and adjacent tissues was detected by Western blot analysis. Spearman’s correlation was performed to elucidate the relationship of NOX2 with VEGF and EGFR. The Kaplan-Meier method was used to calculate survival time, and the log-rank test was used to evaluate differences in survival. Cox‘s proportional hazards regression model was applied in a stepwise manner to analyze the independent prognostic factors.

RESULTS: NOX2 exhibited positive expression in 47.2% (58/123) of the gastric cancer tissues. Western blot analysis revealed that NOX2 was up-regulated in tumor tissues compared to the adjacent tissue [39.0% (48/123)]. Immunohistochemistry staining revealed that CD68, which is a specific marker of macrophages, and NOX expression presented a similar localization and staining intensity. The expression of NOX2 was positively correlated with that of VEGF and EGFR. Comparison of the 5-year survival rates of the NOX2 positive and NOX2 negative groups showed that the NOX2 positive group presented a poor prognosis.

CONCLUSION: NOX2 positively correlates with the levels of VEGF and EGFR. NOX2 may be used as a new biomarker and a potential therapeutic target for gastric cancer.

Keywords: NADPH oxidase 2, Macrophages, Vascular endothelial growth factor, Epidermal growth factor receptor, Prognosis, Survival time

Core tip: In this article, the authors used immunohistochemistry to analyze the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) in formalin-fixed paraffin-embedded tissues from 123 gastric cancer patients. Western blot analysis was employed to examine NOX2 expression in tumor and adjacent tissues. NOX2 was up-regulated in tumor tissues. NOX2 was positively correlated with vascular endothelial growth factor and epidermal growth factor receptor. The results also showed that patients who were NOX2 positive clearly presented worse outcomes than NOX2-negative patients. The expression of NOX2 could be used as a prognostic biomarker for gastric cancer.