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The Nrf2/HO-1 axis can be a prognostic factor in clear cell renal cell carcinoma

Authors Deng Y, Wu Y, Zhao P, Weng W, Ye M, Sun H, Xu M, Wang C

Received 19 September 2018

Accepted for publication 3 January 2019

Published 7 February 2019 Volume 2019:11 Pages 1221—1230

DOI https://doi.org/10.2147/CMAR.S188046

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Yu Deng,1,2,* Yong Wu,2,3,* Ping Zhao,4 Weiwei Weng,1,2 Min Ye,1,2 Hui Sun,1,2 Midie Xu,1,2 Chaofu Wang4

1Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Gynaecologic Oncology, Fudan University Shanghai Cancer Centre, Shanghai, China; 4Department of Pathology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

*These authors contributed equally to this work

Objective: To study the protein expression level of Nrf2/HO-1 in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissue and to explore its relationship with clinicopathological characteristics and prognosis in ccRCC patients.
Materials and methods: In total, 152 ccRCC patients with available follow-up and clinical data were enrolled, and sample microarrays were prepared for immunohistochemistry studies. The human ccRCC cell lines 786-O, OS-RC-2, A498, and ACHN were cultured for immunofluorescence. The protein concentrations of five ccRCC patients’ tumor and adjacent normal renal tissues were prepared for Western blotting. Chi-squared tests, Fisher’s exact test, Kaplan–Meier analyses, log-rank tests, and Cox regression were performed for statistical analyses.
Results: The immunoreactivity results showed that the Nrf2 and HO-1 proteins were found in consistent locations in vitro and were expressed both in ccRCC and adjacent normal tissues. The two proteins were localized in the cytoplasm and nucleus of RCC tumor cells and in adjacent normal tissue cells. The expression levels of Nrf2 and HO-1 were significantly higher in ccRCC tissues than in the adjacent normal tissues. The Nrf2 protein level was found to be significantly correlated with the tumor size. Additionally, higher protein expression levels of Nrf2 and HO-1 were also correlated with worse overall survival outcomes and could potentially be used to predict the prognosis of ccRCC patients.
Conclusion: Our study provides an important theoretical basis for evaluating the clinical prognosis of ccRCC patients, which implies that the Nrf2/HO-1 axis can be a prognostic factor in ccRCC.

Keywords: ROS, Nrf2, HO-1, immunohistochemistry, prognosis
 

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