Abstract
ObjectivesEpithelial-mesenchymal transition (EMT) and the histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2) are important regulators of lung cancer progression and metastasis. Although recent studies support the correlation between EZH2 expression and EMT, no reports have investigated their association using immunohistochemistry or explored their prognostic impact on lung adenocarcinoma. The aim of this study was to elucidate the association between EZH2 and EMT, and their prognostic significance.MethodsEZH2 and the EMT markers E-cadherin and Vimentin were examined by IHC in lung adenocarcinoma specimens that were resected from 2003–2012. Associations between EZH2 and EMT markers and their correlations with survival were analyzed.ResultsWe enrolled 350 patients, approximately 70% of whom were diagnosed as pathological stage I. The rates of positive E-cadherin, Vimentin, and EZH2 expression were 60.3%, 21.4%, and 52.0%, respectively. There was a significant positive correlation between EZH2 and Vimentin expression (p = 0.008), and EZH2 scores were higher in the Mesenchymal group (p = 0.030). In multivariate analysis, EZH2 was an independent predictor of Vimentin expression, and vice versa. EMT and EZH2 overexpression were significantly correlated with poor disease-free and overall survival. Furthermore, the Epithelial group with high EZH2 expression had significantly worse disease-free and overall survival. Positive staining for EMT markers was unfavorable regarding disease-free survival among patients with low EZH2 expression.ConclusionsEMT and high EZH2 expression were associated with poor NSCLC prognoses. Vimentin is a key factor linking EMT and EZH2 in lung adenocarcinoma.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide
Epithelial-mesenchymal transition (EMT) and Enhancer of Zeste Homologue 2 (EZH2) overexpression were significantly correlated with poor disease-free and overall survival
Positive staining for EMT markers was unfavorable regarding disease-free survival among patients with low EZH2 expression
Summary
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing 85% of all cases, and is classified into several subtypes, including adenocarcinoma and squamous cell carcinoma[1]. Immune checkpoint inhibitors have emerged as a novel therapeutic strategy for NSCLC[4, 5]. Therapeutic options for NSCLC have changed dramatically, and prognoses have improved compared with previous decades. E-cadherin is an epithelial marker that maintains cell-cell adhesion and inhibits cell invasion[6]. The mesenchymal marker Vimentin maintain intracellular mechanical homeostasis by mediating cytoskeleton architecture and the balance of cell force generation during EMT in cancer cells[7]. The genetic and epigenetic alterations that occur as cancer cells undergo EMT are currently being elucidated
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