DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon

Abstract

Aim. To detect the expression of dual oxidase (DUOX) 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC). Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC) and real-time quantitative PCR (qPCR). The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified. Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II–IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable. Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues.

High Immunoreactivity of DUOX2 Is Associated With Poor Response to Preoperative Chemoradiation Therapy and Worse Prognosis in Rectal Cancers

“…By immunohistochemistry, overexpression of DUOX2 was observed in the majority of colon cancers (62%), breast cancers (66%), non-small cell lung cancers (86%) and prostate cancers (92%) 15 . In a later study, both mRNA and protein levels of DUOX2 revealed significant up-regulation in gastric and colorectal cancers compared with adjacent normal tissue (all P ≤ 0.01) 16 . High expression of DUOX2 was also an independent prognosticator predicting both lower recurrent-free and overall survival rates in patients with hepatocellular carcinoma after hepatectomy 17 .…”

Dual oxidase: a novel therapeutic target in allergic disease

“…Overexpression of DUOX2/DUOXA2 during ulcerative colitis is thought to be responsible for oxidative DNA damage as a predisposing factor for development of colon cancer (MacFie et al ., ). Indeed, DUOX2 is often overexpressed in cancers of the alimentary tract, including colorectal cancers, and may contribute to cancer progression (Wu et al ., ; Qi et al ., ), suggesting that pharmacological inhibitors with selectivity towards DUOX2 may have clinical utility in anticancer treatment (Lu et al ., ). Recent studies also indicated a potential contribution of DUOX1 in promoting oxidative DNA damage and genomic instability in the thyroid in response to ionizing radiation, as a potentially important contributing feature to thyroid cancer (Ameziane‐El‐Hassani et al ., ).…”

Paradoxical roles of dual oxidases in cancer biology

“…These mucosal surface cell types typically express high levels of unique NOX isoforms, the dual oxidases DUOX1 and/or DUOX2. Analogous to other NOXes, several studies have highlighted that DUOX2 mRNA and protein is often overexpressed in colorectal cancers[105, 106], pancreatic adenocarcinoma [107, 108], Barrett esophagus [105], and gastric cancers[105]. Using a newly developed monoclonal antibody against DUOX2, increased immunohistochemical staining was observed in various tumor types, including prostate, lung, breast, and colon [109].…”