Clinicopathological significance of nuclear factor erythroid-2-related factor 2 Nrf2 expression in gastric cancerReport as inadecuate

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BMC Cancer

, 15:5

Clinical oncology


BackgroundThe transcription factor nuclear factor erythroid-2–related factor 2 Nrf2 was originally identified as a critical regulator of intracellular anti-oxidants and of phase II detoxification enzymes through its transcriptional up-regulation of many anti-oxidant response element ARE-containing genes. Nrf2 protects not only normal cells but also cancer cells from cellular stress, and enhances cancer cell survival. Some studies have shown that Nrf2 expression in cancer patients has clinical significance. However, there has been no comprehensive analysis of the nuclear expression level of Nrf2 in gastrointestinal cancer cells. In this study we aimed to immunohistochemically evaluate the expression of Nrf2, and to assess its clinical significance in gastric cancer.

MethodsA total of 175 gastric cancer patients who received R0 gastrectomy with standard lymph node dissection were enrolled. We immunohistochemically evaluated Nrf2 expression in the paraffin-embedded surgically resected specimens of these 175 patients. Group differences were analyzed using the χ test, Fisher’s exact test, and the Mann–Whitney U test. Associations between Nrf2 expression and clinicopathological features, including clinical outcome, were assessed using univariate and multivariate analyses, and Kaplan-Meier curves with the log-rank test, respectively.

ResultsNrf2 immunoreactivity was predominantly identified in the nucleus of gastric cancer cells. Nrf2 positivity was closely associated with tumor size, tumor depth, lymph node metastases, lymphovascular invasion, histology and stage p < 0.05 for all. A log-rank test indicated that the overall survival of the Nrf2-positive group was significantly poorer than that of the Nrf2-negative group p < 0.01. And, positive Nrf2 expression was significantly associated with resistance to 5FU-based adjuvant chemotherapy p = 0.024.

ConclusionsNrf2 expression was positively associated with aggressive tumor behavior in gastric cancer. This result suggests that Nrf2 expression in gastric cancer is a potential indicator of worse prognosis.

KeywordsNF-E2-related factor 2 Gastric cancer Antioxidants AbbreviationsNrf2NF-E2-related factor 2

OSOxidative stress

Keap 1Kelch-like ECH-associated protein 1

AREantioxidant response element

FBSFetal bovine serum

PBSPhosphate buffered saline

TBSTris-buffered saline

TBSTTBS-Tween 20


ROSReactive oxygen species

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Author: Yota Kawasaki - Sumiya Ishigami - Takaaki Arigami - Yoshikazu Uenosono - Shigehiro Yanagita - Yasuto Uchikado - Yoshiaki Ki


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