title: USP22 promotes tumor progression and induces epithelial-mesenchymal transition in lung adenocarcinoma.
abstract: OBJECTIVE
  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.
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. Electronic address: hujing@ems.hrbmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Oncological Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yang
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Meng
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pang
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. Electronic address: liuyanlong1979@163.com.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The 4th Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. Electronic address: caili@ems.hrbmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
chemical_list: D053773:Transforming Growth Factor beta1; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human
keywords: EMT; Lung adenocarcinoma; Prognosis; TGF-β1; USP22