The association and prognostic impact of enhancer of zeste homologue 2 expression and epithelial–mesenchymal transition in resected lung adenocarcinoma

Taichi Matsubara, Gouji Toyokawa, Kazuki Takada, Fumihiko Kinoshita, Yuka Kozuma, Takaki Akamine, Mototsugu Shimokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Masaki Mori

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Epithelial-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. Methods EZH2 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. Results We 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. Conclusions EMT and high EZH2 expression were associated with poor NSCLC prognoses. Vimentin is a key factor linking EMT and EZH2 in lung adenocarcinoma.

Original languageEnglish
Article numbere0215103
JournalPloS one
Volume14
Issue number5
DOIs
Publication statusPublished - May 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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