Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2016 Volume 14 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2016 Volume 14 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features

  • Authors:
    • Changjiang Li
    • Haitao Wu
    • Shuyi Wang
    • Jiaxing Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Otorhinolaryngology‑Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China, Department of Pathology, Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5171-5179
    |
    Published online on: November 1, 2016
       https://doi.org/10.3892/mmr.2016.5913
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study aimed specifically investigate the expression and correlation of kelch-like ECH-associated protein‑1 (KEAP1), nuclear factor (erythroid-derived 2)‑like 2 (NRF2), quinone oxidoreductase‑1 (NQO‑1) and heme oxygenase‑1 (HO‑1) in laryngeal cancer and their association with clinicopathological features. A total of 33 paired human fresh advanced laryngeal cancer and adjacent normal specimens were collected following total laryngectomy. Immunohistochemical and immunoblotting analysis were performed to evaluate the expression of KEAP1, NRF2, NQO‑1 and HO‑1. All of the patients clinicopathologic features were collected. Immunohistochemistry indicated that NRF2‑positive staining was as high as 79% (26/33) in the cancer samples and predominantly located in the nuclei, whereas positive expression of KEAP1, NQO‑1 and HO‑1 was detected in 70% (23/33), 76% (25/33) and 82% (27/33) of cancer tissues, respectively, and primarily expressed in the cytoplasm. The corresponding adjacent normal samples produced almost no or weak expression of the proteins. There were significant differences in protein expression between the two groups (P<0.01). Immunoblotting analysis also demonstrated that their expression levels were higher in cancer tissue compared with adjacent normal tissue. Notably, KEAP1, NQO‑1 and HO‑1 expression was positively correlated with nuclear NRF2 in cancer tissues, whereas they had no correlation with age, tumor stage (clinical stage III and IV), tumor size and lymph node metastasis. In conclusion, increased expression of NRF2, KEAP1, NQO‑1 and HO‑1 were common in advanced laryngeal cancer. Evaluation of these factors may have important clinical significance for the diagnosis and treatment of this disease.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Harrington KJ, Nutting CM and Pandha HS: Gene therapy for head and neck cancer. Cancer Metastasis Rev. 24:147–164. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

4 

American Society of Clinical Oncology, ; Pfister DG, Laurie SA, Weinstein GS, Mendenhall WM, Adelstein DJ, Ang KK, Clayman GL, Fisher SG, Forastiere AA, et al: American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. J Clin Oncol. 24:3693–3704. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Cho HY, Reddy SP and Kleeberger SR: Nrf2 defends the lung from oxidative stress. Antioxid Redox Signal. 8:76–87. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Inci E, Civelek S, Seven A, Inci F, Korkut N and Burçax G: Laryngeal cancer: In relation to oxidative stress. Tohoku J Exp Med. 200:17–23. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Jaramillo MC and Zhang DD: The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 27:2179–2191. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Singh A, Boldin-Adamsky S, Thimmulappa RK, Rath SK, Ashush H, Coulter J, Blackford A, Goodman SN, Bunz F, Watson WH, et al: RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. Cancer Res. 68:7975–7984. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Khor TO, Huang MT, Prawan A, Liu Y, Hao X, Yu S, Cheung WK, Chan JY, Reddy BS, Yang CS and Kong AN: Increased susceptibility of NRF2 knockout mice to colitis-associated colorectal cancer. Cancer Prev Res (Phila). 1:187–191. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Edge SB and Compton CC; The American Joint Committee on Cancer, : The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Li CJ, Wang SZ, Wang SY and Zhang YP: Assessment of the effect of local application of amifostine on acute radiation-induced oral mucositis in guinea pigs. J Radiat Res. 55:847–854. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Manne U, Myers RB, Moron C, Poczatek RB, Dillard S, Weiss H, Brown D, Srivastava S and Grizzle WE: Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer. 74:346–358. 1997. View Article : Google Scholar : PubMed/NCBI

13 

Piyathilake CJ, Bell WC, Oelschlager DK, Heimburger DC and Grizzle WE: The pattern of expression of Mn and Cu-Zn superoxide dismutase varies among squamous cell cancers of the lung, larynx, and oral cavity. Head Neck. 24:859–867. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Han Y and Chen JZ: Oxidative stress induces mitochondrial DNA damage and cytotoxicity through independent mechanisms in human cancer cells. Biomed Res Int 825065. 2013. View Article : Google Scholar

15 

McLean LS, Watkins CN, Campbell P, Zylstra D, Rowland L, Amis LH, Scott L, Babb CE, Livingston WJ, Darwanto A, et al: Aryl hydrocarbon receptor ligand 5F 203 induces oxidative stress that triggers DNA damage in human breast cancer cells. Chem Res Toxicol. 28:855–871. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Dwivedi R, Raturi D, Kandpal N, Dwivedi R, Singh R and Puri V: Oxidative stress in patients with laryngeal carcinoma. Indian J Cancer. 45:97–99. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Dinkova-Kostova AT, Holtzclaw WD and Kensler TW: The role of Keap1 in cellular protective responses. Chem Res Toxicol. 18:1779–1791. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Kensler TW and Wakabayashi N: Nrf2: Friend or foe for chemoprevention? Carcinogenesis. 31:90–99. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Lee JM and Johnson JA: An important role of NRF2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol. 37:139–143. 2004.PubMed/NCBI

20 

Stacy DR, Ely K, Massion PP, Yarbrough WG, Hallahan DE, Sekhar KR and Freeman ML: Increased expression of nuclear factor E2 p45-related factor 2 (NRF2) in head and neck squamous cell carcinomas. Head Neck. 28:813–818. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Huang CF, Zhang L, Ma SR, Zhao ZL, Wang WM, He KF, Zhao YF, Zhang WF, Liu B and Sun ZJ: Clinical significance of KEAP1 and NRF2 in oral squamous cell carcinoma. PLoS One. 8:e834792013. View Article : Google Scholar : PubMed/NCBI

22 

Solis LM, Behrens C, Dong W, Suraokar M, Ozburn NC, Moran CA, Corvalan AH, Biswal S, Swisher SG, Bekele BN, et al: Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin Cancer Res. 16:3743–3753. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Liao H, Zhou Q, Zhang Z, Wang Q, Sun Y, Yi X and Feng Y: NRF2 is overexpressed in ovarian epithelial carcinoma and is regulated by gonadotrophin and sex-steroid hormones. Oncol Rep. 27:1918–1924. 2012.PubMed/NCBI

24 

Soini Y, Eskelinen M, Juvonen P, Kärjä V, Haapasaari KM, Saarela A and Karihtala P: Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma. Pathol Res Pract. 210:35–39. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M, Suzuki T, Kobayashi A, Yokota J, Sakiyama T, et al: Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 68:1303–1309. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Konstantinopoulos PA, Spentzos D, Fountzilas E, Francoeur N, Sanisetty S, Grammatikos AP, Hecht JL and Cannistra SA: Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer. Cancer Res. 71:5081–5089. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Yoo NJ, Kim HR, Kim YR, An CH and Lee SH: Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology. 60:943–952. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Wang J, Zhang M, Zhang L, Cai H, Zhou S, Zhang J and Wang Y: Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival. J Surg Res. 164:e99–e105. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li C, Wu H, Wang S and Zhu J: Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features. Mol Med Rep 14: 5171-5179, 2016.
APA
Li, C., Wu, H., Wang, S., & Zhu, J. (2016). Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features. Molecular Medicine Reports, 14, 5171-5179. https://doi.org/10.3892/mmr.2016.5913
MLA
Li, C., Wu, H., Wang, S., Zhu, J."Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features". Molecular Medicine Reports 14.6 (2016): 5171-5179.
Chicago
Li, C., Wu, H., Wang, S., Zhu, J."Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features". Molecular Medicine Reports 14, no. 6 (2016): 5171-5179. https://doi.org/10.3892/mmr.2016.5913
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Wu H, Wang S and Zhu J: Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features. Mol Med Rep 14: 5171-5179, 2016.
APA
Li, C., Wu, H., Wang, S., & Zhu, J. (2016). Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features. Molecular Medicine Reports, 14, 5171-5179. https://doi.org/10.3892/mmr.2016.5913
MLA
Li, C., Wu, H., Wang, S., Zhu, J."Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features". Molecular Medicine Reports 14.6 (2016): 5171-5179.
Chicago
Li, C., Wu, H., Wang, S., Zhu, J."Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features". Molecular Medicine Reports 14, no. 6 (2016): 5171-5179. https://doi.org/10.3892/mmr.2016.5913
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team