Nuclear β-catenin accumulation is associated with increased expression of Nanog protein and predicts poor prognosis of non-small cell lung cancer

Background: Although the prognostic roles of beta-catenin expression in non-small cell lung cancer (NSCLC) have been reported in several immunohistochemical (IHC) studies, the results were not consistent because some studies lack sufficient number of the positive cases or did not evaluate the subcellular localization features of the protein. Method: In this study, we have evaluated the expression levels and subcellular localization of beta-catenin and Nanog proteins IHC staining in tissue specimens from 309 patients with NSCLC, and explored their association with clinicopathological features and patient outcome. Results: We showed that patients with negative expression of membranous beta-catenin had a trend towards shorter survival (p=0.064) than those with positive expression. In contrast to previous studies, we found that increased expression of either cytoplasmic or nuclear beta-catenin was strongly associated with poor prognosis and was an independent prognosticator for overall survival (p <0.01). We further found that NSCLC cells frequently exhibited an abundance of nuclear Nanog protein which was significantly correlated with nuclear beta-catenin expression (p <0.01) and poor prognosis (p <0.01). Interestingly, immunofluorescent staining results revealed that increased expression of Nanog and nuclear translocation of beta-catenin occurred concomitantly in response to epidermal growth factor receptor (EGFR) signaling in A549 and H23 cells. Furthermore, western blot analysis show that nuclear beta-catenin rather than cytoplasmic beta-catenin expression in the A549 and H23 cells can be enhanced by adding EGF, Nanog expression in the A549 and H23 cells with knockdown of beta-catenin can not be obviously enhanced by adding EGF. Conclusion: We propose that evaluation of subcellular localization of beta-catenin and Nanog expression is of clinical significance for patients with NSCLC.