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Ann Surg Oncol. 2014 Jul;21(7):2347-52. doi: 10.1245/s10434-014-3600-2. Epub 2014 Mar 6.

Nrf2 is useful for predicting the effect of chemoradiation therapy on esophageal squamous cell carcinoma.

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Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan.



The transcription factor NF-E2-related factor 2 (Nrf2) was originally identified to be a critical regulator of intracellular antioxidants and phase II detoxification enzymes. Recent studies have shown that high Nrf2 expression gives cancer cells an advantage for survival from anticancer chemotherapy and radiation therapy. The aims of this retrospective study were to examine the expression of Nrf2 in biopsy specimens of esophageal squamous cell carcinoma (ESCC) and to evaluate whether such expression is useful for predicting the response to chemoradiation therapy (CRT).


A total of 46 patients with ESCC who received curative surgery after CRT from 1997 to 2011 were enrolled in the current study. Nrf2 expression in the biopsy specimens before CRT was examined immunohistochemically using anti-Nrf2 antibody. The correlations between Nrf2 expression and clinical factors and histological and clinical response to CRT were analyzed.


The rate of Nrf2-positive expression was 39 %. Both clinically and histologically, significant correlations were found between positive Nrf2 expression and unfavorable response to CRT. Furthermore, Nrf2 was significantly correlated with clinical lymph node metastases and patients' postoperative outcomes. Multivariate analysis showed that Nrf2 expression status was an independent prognostic factor.


Nrf2 expression was found to be closely related to the effect of CRT and could predict the CRT outcome in patients with ESCC.

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