The role of NF-E2-related factor 2 in predicting chemoresistance and prognosis in advanced non-small-cell lung cancer

Clin Lung Cancer. 2011 May;12(3):166-71. doi: 10.1016/j.cllc.2011.03.012. Epub 2011 Apr 28.

Abstract

Background: NF-E2-related factor 2 (Nrf2) plays an important role in platinum chemoresistance by activating transcription of target genes through binding to the antioxidant response element (ARE) in gene promoters, moreover it could stimulate tumor growth in non-small-cell lung cancer (NSCLC). The objective of this study was to elucidate the correlation between Nrf2 expression and platinum-based chemotherapy response as well as the prognostic significance of Nrf2 levels.

Patients and methods: Immunohistochemical analysis of Nrf2 in tumor specimens was performed in a total of 60 patients with stage IIIB or IV NSCLC.

Results: Positive staining for Nrf2 was found in nearly all cases, just at different levels. High Nrf2 expression was noted in 34 of 60 patients (56.7%). The expression of Nrf2 correlated with age (P = .014), stage (P = .017), and performance status (P = .014). The response rate of platinum-based chemotherapy in patients with < 75% positive staining was significantly higher than that in patients with 75%-100% positive staining (P = .003; r = 0.447). Furthermore, a high percentage of Nrf2 staining was the independent prognostic factor in progression survival (P = .000) analysis.

Conclusion: We suggest that the assessment of Nrf2 expression may be useful for evaluating chemoresistance and tumor progression in patients with advanced stage NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / analysis
  • NF-E2-Related Factor 2 / physiology*
  • Neoplasm Staging
  • Prognosis
  • Survival Rate

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human