NADPH oxidase 4 is correlated with gastric cancer progression and predicts a poor prognosis

Am J Transl Res. 2019 Jun 15;11(6):3518-3530. eCollection 2019.

Abstract

NADPH oxidase 4 (NOX4) is one of the main sources of reactive oxygen species, and plays a crucial role in the occurrence and development of tumors. However, there is currently little evidence demonstrating that NOX4 expression is associated with gastric cancer. To establish whether NOX4 plays a role in gastric cancer progression and prognosis, we performed immunohistochemistry on gastric cancer tissues and paired adjacent normal tissues from 90 gastric cancer patients to detect and compare NOX4 expression. Next, we analyzed the association between NOX4 expression and clinicopathological characteristics. Survival analysis was performed to explore the association between NOX4 expression and the prognosis of gastric cancer patients. Furtherly, we investigated the effect of NOX4-knockdown using siRNA on gastric cancer progression in vitro and in vivo. Our results revealed that NOX4 expression in gastric cancer tissues is higher than in paired adjacent normal tissues (P = 0.0009). NOX4 expression is significantly correlated with tumor size (P = 0.0321), lymphatic metastasis (P = 0.0125) and vascular invasion (P = 0.0017) and a poor prognosis (P = 0.0000) in gastric cancer patients. NOX4 depletion could significantly inhibit the invasion, proliferation, EMT and MMP7 expression of gastric cancer cells and suppress the progression of gastric cancer in vivo. In conclusion, NOX4 is related to gastric cancer development and predicts a poor prognosis. NOX4 may play an essential role in the progression of gastric cancer, and is a promising target for the prevention and treatment of gastric cancer.

Keywords: NOX4; gastric cancer; prognosis; progression; reactive oxygen species.