title: Down-regulation of PAX6 by promoter methylation is associated with poor prognosis in non small cell lung cancer.
abstract: BACKGROUND
  Promoter methylation is an alternative mechanism of gene silencing in human tumorigenesis. Although a number of methylated genes have been found in non small cell lung cancer (NSCLC), useful methylation markers for early prognostic evaluation of NSCLC remain largely unknown.
  
  
  METHODS
  Using methylation-specific PCR (MSP), we examined promoter methylation status of PAX6 gene, and explored their association with clinical features in NSCLC via chi-square test. NSCLC patient survival was assessed by Kaplan-Meier analyses and a Cox proportional hazard model was employed for multivariate analyses.
  
  
  RESULTS
  The methylation level of PAX6 gene was higher in tumor tissues than that in normal tissues. In addition, PAX6 promoter methylation showed a very significant correlation with differentiation (P = 0.002), distant metastasis (P = 0.024), and TNM stage (P = 0.002). PAX6 gene promoter hyper-methylation was found to be significantly associated with poor overall survival (P = 0.018) and to serve as an independent marker for prognosis using multivariate Cox regression analysis (HR: 2.254, 95% CI: 1.088-4.667, P = 0.029).
  
  
  CONCLUSIONS
  We found that PAX6 gene was specifically methylated in NSCLC, and demonstrated the effect of promoter methylation of PAX6 gene on clinical outcome in NSCLC, indicating the methylated PAX6 may be useful biomarkers for prognostic evaluation in NSCLC.
authors.affiliation: Xiangya Hospital of Central South University China.
authors.forename: Xiangxian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Xiangya Hospital of Central South University China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Seven-year Clinical Medicine, Grade 2011, Zhengzhou University China.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Radiotherapy and Severe Tumor Institution, Zhengzhou University China.
authors.forename: Tiansong
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department III of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department III of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University China.
authors.forename: Daoke
authors.initials: D
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000071841:PAX6 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human
keywords: Non-small cell lung cancer; PAX6; methylation; prognosis