Gene expression and prognosis of NOX family members in gastric cancer
Received 4 January 2018
Accepted for publication 27 March 2018
Published 24 May 2018 Volume 2018:11 Pages 3065—3074
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Carlos E Vigil
Xin You,1 Mingzhe Ma,2,3 Guoxin Hou,4 Yumin Hu,2 Xi Shi1
1The First Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; 2State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; 3Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China; 4Department of Oncology, The First Affiliated Hospital of Jiaxing University, Jiaxing, China
Introduction: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) are frequently deregulated in several human malignancies, including gastric cancer (GC). NOX-derived reactive oxygen species have been reported to contribute to gastric carcinogenesis and cancer progression. However, the expression and prognostic role of individual NOX in GC patients remain elusive.
Methods and materials: We investigated genetic alteration and mRNA expression of NOX family in GC patients via the cBioPortal, Human Protein Atlas, and Oncomine databases. Furthermore, we evaluated prognostic value of distinct NOX in GC patients through “The Kaplan–Meier plotter” database.
Results: Our analysis demonstrated that mRNA deregulation of NOX genes was common alteration in GC patients. Compared with normal tissues, NOX1/2/4 mRNA expression levels in GC tissues were higher, while NOX5 and DUOX1/2 expression levels were lower. Importantly, our results indicated that high mRNA expression of NOX2 was associated with better overall survival whereas NOX4 and DUOX1 were correlated with worse overall survival in all GC patients, particularly in intestinal-type GC patients. In addition, our data also shed light on the diverse roles of individual NOX members in GC patients with different clinicopathological features, including human epidermal growth factor receptor 2 status, clinical stages, pathological grades, and different choices of treatments of GC patients.
Conclusion: These findings suggest that individual NOX family genes, especially NOX2/4, and DUOX1, are potential prognostic markers in GC and implicate that the use of NOX inhibitor targeting NOX4 and DUOX1 may be an effective strategy for GC therapy.
Keywords: NADPH oxidases, stomach cancer, online database, prognosis, drug target
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