title: High SOX2 levels predict better outcome in non-small cell lung carcinomas.
abstract: BACKGROUND
  SOX2 is an embryonic developmental transcription factor, which is important in the development of the respiratory tract. SOX2 overexpression is associated with aggressive disease in several tumor types. However, SOX2 overexpression and gene amplification associates with favorable outcome in lung squamous cell carcinomas (SCC) and dissimilar results have been reported in lung adenocarcinomas (ADC). The aim of the present study was to evaluate SOX2 expression in NSCLC and determine the relationship with clinico-pathological variables and outcome.
  
  
  METHODS
  SOX2 protein levels were measured in tissue microarrays (TMAs) containing FFPE samples from two independent lung cancer cohorts (n = 340 & 307) using automated quantitative immunofluorescence (QIF). Assay validation was performed using FFPE preparations of cell lines with known SOX2 expression. Associations of SOX2 levels with main clinico-pathological characteristics and with overall survival were studied using uni-and multivariate analysis.
  
  
  RESULTS
  SOX2 levels were higher in patients with SCC than in ADC in both cohorts (p value<0.0001). In the training cohort, NSCLC patients whose tumors showed high SOX2 (n = 245) had longer survival than those with low SOX2 levels (log rank p = 0.0002). Comparable results were observed in the second independent validation cohort, log rank p = 0.0113. SOX2 positive cases showed a 58% reduction in risk of death in Cox univariate analysis (hazards ratio-HR = 0.42 confidence interval-CI (0.36,0.73), p = 0.0002). SOX2 was associated with significantly longer survival independent of histology in multivariate analysis (hazards ratio-HR = 0.429 confidence interval-CI (0.295, 0.663), p = <0.001).
  
  
  CONCLUSIONS
  SOX2 is an independent positive prognostic marker in NSCLC. Increased SOX2 levels are more frequent in SCC than in ADC, but the association with better survival is independent from the histological subtype.
authors.affiliation: Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut, USA. vamsidhar.velcheti@yale.edu
authors.forename: Vamsidhar
authors.initials: V
authors.lastname: Velcheti
authors.forename: Kurt
authors.initials: K
authors.lastname: Schalper
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Yao
authors.forename: Huan
authors.initials: H
authors.lastname: Cheng
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocoglu
authors.forename: Kavita
authors.initials: K
authors.lastname: Dhodapkar
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Deng
authors.forename: Scott
authors.initials: S
authors.lastname: Gettinger
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D003237:Connecticut; D005260:Female; D005455:Fluorescent Antibody Technique; D006115:Greece; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015203:Reproducibility of Results; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors