title: Prognostic role of Twist, Slug, and Foxc2 expression in stage I non-small-cell lung cancer after curative resection.
abstract: By using immunohistochemistry in tissue microarrays of 137 cases, we evaluated the prognostic power of a 3-marker epithelial-mesenchymal transition–related model in patients with stage I non-small-cell lung cancer who underwent radical surgical resection. The Twist/Slug/Foxc2 coexpression model accurately prognosticated these patients and may be helpful in refining current treatment strategy for stage I non-small-cell lung cancer.
  
  
  BACKGROUND
  Lung cancer is the leading cause of cancer-related death in the world. Only about 60% of patients with stage I non-small-cell lung cancer (NSCLC) can be cured by surgery alone. Current clinical and molecular markers are inadequate prognosticators. We developed a 3-marker model that closely approximates survival probability of patients with stage I NSCLC.
  
  
  METHODS
  Expression of Twist, Slug, and Foxc2 was assessed by immunohistochemistry in tissue microarrays that contained paired tumor and peritumoral lung tissue from 137 patients who underwent surgical resection for stage I NSCLC. The prognostic value of Twist, Slug, and Foxc2, and the cumulative effects of the 3 markers on survival were evaluated.
  
  
  RESULTS
  Increased expression of Twist, Slug, and Foxc2 was observed in 38.0%, 18.2%, and 27.7% of primary tumors, respectively. Overexpression of Twist, Slug, and Foxc2 in stage I NSCLC was associated with a worse overall survival (P = .001, P = .002, P < .001, respectively) and correlated with a shorter recurrence-free survival (P < .001, P = .001, P < .001 respectively). The cumulative influence of these markers on outcome was analyzed; a combination of more than 2 positive markers was an independent predictor of recurrence-free and overall survival (P = .002 and P = .009, respectively).
  
  
  CONCLUSIONS
  The Twist/Slug/Foxc2 model is useful in predicting survival of stage I NSCLC and may be helpful in refining current treatment strategy.
authors.affiliation: Department of Thoracic Surgery, Zhong Shan Hospital, Shanghai Medical School, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Pang
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Ya-Xing
authors.initials: YX
authors.lastname: Shen
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Chen
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Xi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C082078:mesenchyme fork head 1 protein