USP22 promotes tumor progression and induces epithelial-mesenchymal transition in lung adenocarcinoma

Lung Cancer. 2015 Jun;88(3):239-45. doi: 10.1016/j.lungcan.2015.02.019. Epub 2015 Mar 10.


Objectives: Our previous study showed that USP22 as an oncogene may mediate cancer development and progression in NSCLC, but the underlying molecular mechanism remains uncharacterized. Epithelial-mesenchymal transition (EMT) has been reported to play an important role in migration and invasion of the tumor cells. Thus, this study aims to determine the clinical significance and the possible roles of USP22 in EMT and progression of lung adenocarcinoma.

Methods: Immunohistochemistry was used to determine the expression of USP22 in clinical samples. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated by statistical analysis. Moreover, we evaluated whether USP22 could induce EMT in cultured lung cancer cells.

Results: The USP22 expression was positive in 76.03% of specimens and was correlated with advanced clinicopathologic classifications (differentiation, T and AJCC stages) and TGF-β1 expression (p=0.008). Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival and disease-free survival (HR, 2.060; p=0.013 and HR, 1.993; p=0.016). In vitro study revealed that USP22 can regulate proliferation and invasive properties, and induce EMT of lung adenocarcinoma cells. Moreover, USP22 may up-regulate TGF-β1 expression.

Conclusions: Our data indicated that USP22 may promote lung adenocarcinoma cell invasion by the induction of EMT.

Keywords: EMT; Lung adenocarcinoma; Prognosis; TGF-β1; USP22.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Thiolester Hydrolases / genetics
  • Thiolester Hydrolases / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Ubiquitin Thiolesterase


  • Transforming Growth Factor beta1
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase
  • Usp22 protein, human