Elevated Peroxiredoxin 1, but not NF-E2–Related Factor 2, Is an Independent Prognostic Factor for Disease Recurrence and Reduced Survival in Stage I Non–Small Cell Lung Cancer

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Abstract
Lung cancer is the leading cause of cancer death with chance of survival restricted to a subset of non-small cell lung cancer (NSCLC) patients able to undergo surgical resection. However, the recurrence rate of NSCLC after surgery remains high with few prognostic indicators of clinical outcome. Peroxiredoxin1 (Prx1) is shown to be elevated in various cancers and confers an aggressive survival phenotype. We recently cloned the prx1 promoter and found that NF-E2-related factor 2 (Nrf2) is a key transcription factor for prx1 up-regulation. Previous studies suggest that Nrf2 may be constitutively activated in NSCLC. Based on the above information, we investigated whether Prx1 and/or Nrf2 levels have prognostic significance in stage I NSCLC. Immunohistochemical expression of Prx1 and Nrf2 was evaluated in paraffin-embedded tissues from 90 patients who underwent a curative surgical resection. Increased expression of cytosolic Prx1 (66.7%) and nuclear Nrf2 (61.8%) was observed in this series. Prx1 elevation, but not Nrf2, correlated with reduced recurrence-free survival and overall survival on univariate (P = 0.01 and P = 0.03) and multivariate (P = 0.003 and P = 0.005) analyses. This is the first study to test the prognostic significance of Prx1 and Nrf2 in human cancers. Our results show that Prx1 expression status predicts for recurrence and shorter survival in stage I NSCLC after surgery. Considering the possible role of Prx1 and Nrf2 in radioresistance/chemoresistance, it warrants future investigation to evaluate whether elevated Prx1 and/or Nrf2 levels are predictive of treatment response in advanced lung cancer and other malignancies.