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Correlation Between Nuclear Factor E2-Related Factor 2 Expression and Gastric Cancer Progression

Hongyu Zheng, Zhiwei Nong, Guohao Lu

Department of Ultrasound, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China (mainland)

Med Sci Monit 2015; 21:2893-2899

DOI: 10.12659/MSM.894467

Available online:

Published: 2015-09-27

BACKGROUND: Nuclear factor E2-related factor 2 (Nrf2) plays an anti-oxidative and phase II detoxification function via its up-regulation on various antioxidant response elements (ARE) genes. Nrf2 can protect both normal and cancer cells from damages of cell stress, thereby exerting a critical role in the development of cancer. The expression and significance of Nrf2 in gastric cancer, however, has not been reported. This study thus aimed to investigate the expression of Nrf2 in gastric cancer tissues via immunohistochemical (IHC) staining.
MATERIAL AND METHODS: Gastric carcinoma tissues from a total of 175 patients during surgical resection were examined for Nfr2 expression profiles using IHC staining on paraffin-embedded slides. Between-group-comparisons were performed by chi-square, Fisher’s exact, or Mann-Whitney U test. The correlation between Nfr2 expression and clinical indexes was further analyzed by Kaplan-Meier test, univariate/multivariate analysis, and log-rank test.
RESULTS: Nrf2 is mainly expressed in nuclei of gastric carcinoma tissues, with significant correlation with clinical indexes, including tumor size, invasive depth, lymph node metastasis, and invasion. Patients with Nrf2-positive expression had significantly lower survival rates compared to those in the negative group (p<0.01), with chemo-resistance against 5-fluorouracil (5-FU) (p<0.05).
CONCLUSIONS: Nrf2 expression is positively correlated with invasive gastric cancer, suggesting its utility as a predictive index for unfavorable prognosis.

Keywords: Aged, 80 and over, Adult, Antineoplastic Agents - therapeutic use, Antioxidants - chemistry, Carcinoma - metabolism, Drug Resistance, Neoplasm, Fluorouracil - therapeutic use, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Kaplan-Meier Estimate, Lymphatic Metastasis, Multivariate Analysis, NF-E2-Related Factor 2 - metabolism, Neoplasm Invasiveness, Prognosis, Response Elements, Stomach Neoplasms - metabolism, Up-Regulation