Abstract
BackgroundAlthough the prognostic roles of β-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.MethodIn this study, we have evaluated the expression levels and subcellular localization of β-catenin and Nanog proteins IHC staining in tissue specimens from 309 patients with NSCLC, and explored their association with clinicopathological features and patient outcome.ResultsWe 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 β-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 β-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 β-catenin occurred concomitantly in response to epidermal growth factor receptor(EGFR) signaling in A549 and H23 cells. Furthermore, western blot analysis show that nuclear β-catenin rather than cytoplasmic β-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 β-catenin can not be obviously enhanced by adding EGF.ConclusionWe propose that evaluation of subcellular localization of β-catenin and Nanog expression is of clinical significance for patients with NSCLC.
Highlights
Lung cancer is the most common cancer worldwide, and has the highest incidence and mortality levels of any cancer [1]
In the absence of Wnt signal, cytoplasmic β-catenin interacts with glycogen synthase kinase-3β (GSK-3β) in a large complex known as destruction complex which contains the adenomatous polyposis coli (APC) and the axis inhibition protein (Axin)
We have evaluated the expression levels and subcellular localization of β-catenin and Nanog proteins in primary tumor specimens from 309 patients with non-small cell lung cancer (NSCLC), and explored their association with clinicopathological features and patient outcome
Summary
Lung cancer is the most common cancer worldwide, and has the highest incidence and mortality levels of any cancer [1]. NSCLC is thought to originate in lung epithelial cells, and comprises diverse histological subtypes including adenocarcinoma, bronchioloalveolar, squamous, anaplastic and large-cell carcinomas, β-catenin is a key component of the canonical Wnt pathway that plays pivotal roles in pattern formation during embryogenesis and in malignant transformation [5]. In the absence of Wnt signal, cytoplasmic β-catenin interacts with glycogen synthase kinase-3β (GSK-3β) in a large complex known as destruction complex which contains the adenomatous polyposis coli (APC) and the axis inhibition protein (Axin). When Wnt pathway is activated, β-catenin phosphorylation by GSK-3β is inhibited. The prognostic roles of β-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
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